Tag /

Immune System

Episodes

rhonda
Premium

Q&A #64 with Dr. Rhonda Patrick (11/2/24)

Posted on November 19th 2024 (7 months)

Dr. Rhonda Patrick discusses silicone safety, grounding, pentadecanoic acid, and the potential benefits of olive leaf extract and peptides.

sleep

How Heat Therapy Improves Slow Wave Sleep

Posted on May 30th 2023 (about 2 years)

Heat therapy (saunas, exercise, hot baths) can enhance slow-wave sleep. This video explores exercise and heat's joint role in sleep regulation.

ketogenic diet

The ketogenic diet and cancer research | Dominic D'Agostino

Posted on May 21st 2022 (about 3 years)

In this clip, Dr. Dominic D'Agostino discusses the implications of adding a ketogenic diet to cancer treatment protocols.

Topic Pages

  • Blood-brain barrier

    Blood-brain barrier regulates CNS immune surveillance by limiting leukocyte transmigration and selectively transporting cytokines and antibodies.

  • Breast milk and breastfeeding

    Breast milk delivers maternal antibodies, immune cells, and cytokines that passively protect infants and shape neonatal immune maturation.

  • Butyrate

    Microbiota-derived butyrate modulates immune homeostasis by HDAC inhibition, enhancing colonic regulatory T-cell differentiation and anti-inflammatory cytokine production.

  • Cold exposure

    Cold exposure stimulates sympathetic-adrenal catecholamine release and brown-adipose thermogenesis, collectively altering leukocyte trafficking and proinflammatory cytokine profiles.

  • Omega-3 fatty acids

    Omega-3 PUFA-derived resolvins and maresins suppress pro-inflammatory cytokine production, thereby modulating innate and adaptive immune responses.

  • Thymic involution

    Age-associated thymic involution diminishes thymopoiesis, thereby reducing naïve T-cell repertoire and weakening systemic adaptive immunity.

  • Toll-like receptors

    Toll-like receptors initiate innate immune signaling by recognizing pathogen-associated molecular patterns and activating downstream NF-κB-mediated cytokine production.

News & Publications

  • Working night shifts and accumulating sleep debt increase nurses' susceptibility to illnesses, with risk escalating by nearly 50% for frequent night shift workers. www.tandfonline.com
    Sleep Immune System Circadian Rhythm

    Shift work keeps essential services operating, but often at a cost to workers' health. Nurses, who frequently work irregular hours, may be particularly susceptible to disrupted sleep and weakened immune function. A recent study found that sleep debt and night shift work may elevate nurses' risk of common infections by as much as 50%.

    Researchers analyzed data from more than 1,300 nurses (average age, 42 years). Participants reported their typical sleep duration, how much sleep they needed, whether they worked night shifts, and how often they experienced infections, such as colds, pneumonia, sinusitis, or gastrointestinal infections, over the previous three months. The researchers used statistical methods to examine links between sleep patterns, shift schedules, and infection risk while accounting for age, sex, and whether the nurses had children at home.

    Nurses with greater sleep debt faced a higher risk of multiple infections. Those who slept one to two hours less than necessary were about 30% more likely to experience a cold, while those with more than two hours of sleep debt had more than double the risk. The risk of pneumonia, bronchitis, sinusitis, and gastrointestinal infections also rose with greater sleep debt. Working night shifts was linked to a 28% higher risk of experiencing a cold, and those with more frequent night shifts were nearly 50% more likely to report having a cold.

    These findings suggest chronic sleep debt and night shift work compromise the immune system, making nurses more susceptible to infections. Learn about practical ways to manage the risks of shift work in this episode featuring Dr. Satchin Panda.

    Read more
  • Regular blood donation promotes beneficial stem cell mutations while minimizing disease risk by inducing genetic changes that preferentially support healthy red blood cell production. ashpublications.org
    Cancer Stem Cells Immune System Genetics

    Donating blood is an act of generosity that saves lives, yet few donors think about how it affects their own health. Each donation triggers a surge in blood cell production, a process that could subtly shape the long-term health of blood-forming stem cells. A recent study found that frequent blood donation promotes the expansion of specific blood stem cell mutations that support healthy red blood cell production.

    Researchers analyzed blood samples from 217 older men who had donated more than 100 times and compared them to 212 men who had donated fewer than 10 times. They looked for clonal hematopoiesis, a condition where blood stem cells acquire genetic changes that allow specific cell populations to expand. They also used gene-editing techniques to study how particular mutations behaved when exposed to erythropoietin, a hormone that increases after blood loss.

    They found that the overall rate of clonal hematopoiesis was similar between frequent and infrequent donors. However, mutations in the DNMT3A gene showed distinct patterns in frequent donors. Some of these mutations responded to erythropoietin by expanding, while others, known to be associated with leukemia, were more likely to grow in response to interferon-gamma, a protein involved in the immune response. Further analysis revealed that the erythropoietin-responsive mutations tended to push blood stem cells toward making more red blood cells rather than leading to abnormal or harmful changes.

    These findings suggest that repeated blood donation encourages the expansion of specific blood stem cell mutations, but the effects support normal blood cell production rather than increase disease risk. Blood donation also lowers levels of iron—a key nutrient that, in excess, harms the brain. Learn more in this episode featuring Dr. Gordon Lithgow.

    Read more
  • Cold-water immersion may offer stress relief and immune benefits, but its effects are highly time dependent. journals.plos.org
    Sleep Inflammation Immune System Mental Health Cold Stress

    Cold-water immersion has surged in popularity, with ice baths and cold showers touted as shortcuts to better health. Advocates claim it improves mood, sharpens focus, and speeds up recovery. A recent study found that while cold exposure temporarily increased inflammation, it reduced stress 12 hours later, improved sleep, and reduced sick days.

    Researchers conducted a systematic review and meta-analysis of 11 studies involving more than 3,100 healthy adults investigating the effects of cold-water exposure on mental and physical health markers, including mood, stress, immunity, inflammation, and sleep quality. Participants in the various studies took cold showers or ice baths at temperatures between 7°C (45°F) and 15°C (59°F) for at least 30 seconds.

    The analysis revealed that inflammation spiked immediately after immersion and stayed elevated for an hour. Interestingly, stress levels dropped 12 hours later but remained unchanged at other time points. Cold exposure did not immediately boost immune function, but a separate analysis linked cold showers to a 29% drop in sickness absence. Participants reported better sleep and overall well-being but no changes in mood.

    These findings suggest that cold-water immersion may offer short-term stress relief and potential immune benefits, with highly time-dependent effects. The effects of cold exposure may be due to hormesis—a compensatory defense response that conditions the body against future stressors. Learn more in Aliquot #97: Thermal Stress, Part II: Unveiling the Power of Cold Exposure on Health and Performance

    Read more
  • Regular cold showers boost immune responses, increasing levels of immunoglobulins and cytokines critical in protecting against infections. www.sciencedirect.com
    Inflammation Immune System Cold Stress

    Cold exposure has long been used in traditional medicine for its many health benefits. However, recent research demonstrates that cold affects the immune system. A new study found that regular cold showers can increase immune cells and antibodies that protect against infections.

    Researchers assigned 60 healthy adults to one of two groups, one taking cold showers (five to 10 minutes at 10° to 15°C, 50° to 59°F) and the other hot showers (40° to 42°C, 104° to 107.6°F) for 90 days. Showers were brief, lasting just five to 10 minutes. They took blood samples at baseline, 30, 60, and 90 days to measure various immune factors, including immunoglobulins, cytokines, and interferon-gamma levels.

    They found that those who took cold showers had considerably higher levels of immunoglobulins (IgG, IgA, and IgM) and cytokines (interleukin-2 and interleukin-4). In contrast, those who took hot showers experienced decreased IgM levels and no marked changes in cytokine levels.

    These findings suggest that regular cold showers boost the body’s immune responses. Cold showers offer a practical and accessible alternative to full cold-water immersion, requiring no specialized equipment beyond a regular shower, and can be taken conveniently at home. Their brief duration minimizes the risk of hypothermia, making them a safer cold exposure option. Learn about the many health benefits of cold exposure in our comprehensive overview article.

    Read more
  • Food antigens, proteins in meat and milk that trigger allergic reactions, activate immune responses that reduce the risk of small intestinal tumors. www.frontiersin.org
    Cancer Diet Immune System Allergies Protein

    Proteins in milk, meat, and other foods can trigger allergic reactions in some people. However, these proteins—called antigens—can also interact with the immune system to suppress small intestinal tumors. A recent study in mice found that food antigens help activate immune responses in the small intestine, potentially reducing the risk of tumors.

    Researchers fed mice genetically prone to developing intestinal tumors—similar to the genetic predisposition to familial adenomatous polyposis in humans—an antigen-free diet to pinpoint the role of food components in immune activation. They also depleted immune tissues in the animals' small intestines called Peyer’s patches to investigate how food antigens trigger immune cells.

    They found that food antigens activate immune cells in Peyer’s patches, suppressing small intestinal tumor formation. This immune response is crucial for maintaining a tumor-suppressive environment in the gut.

    These findings suggest that food antigens help protect against small intestinal tumors in mice by activating immune cells that promote tumor suppression, highlighting their potential as a protective factor in gut health. The microbiome plays a key role in gut health, too. Learn more in this episode featuring Dr. Eran Elinav.

    Read more
  • People with tattoos have a 21% increased risk of malignant lymphoma, with laser tattoo removal further amplifying the risk to 163%. www.thelancet.com
    Cancer Immune System

    Body art is more popular than ever, with roughly one-third of people in the U.S. having at least one tattoo. However, tattoo inks often contain harmful chemicals, including carcinogenic pigments and metals. A recent study found that people with tattoos are 21% more likely to develop malignant lymphoma.

    Researchers conducted a case-control study among roughly 1,400 people diagnosed with malignant lymphoma (“cases”) in people aged 20 to 60 over 10 years. They matched the cases with age- and sex-matched people without cancer (“controls”) from the general population. Then, they gathered information about the participants' tattoo exposure and assessed the relationship between tattoos and lymphoma risk.

    They found that overall, participants with tattoos were 21% more likely to develop malignant lymphoma than those without. The risk of lymphoma among those who had received their first tattoo within the previous two years was 81% higher than those without a tattoo. Risk decreased nearly to baseline between three and 10 years after the first tattoo but increased again to 19% after 11 years, suggesting that long-term exposure to tattoo-related chemicals contributes to a delayed but persistent risk of developing lymphoma.

    Undergoing laser removal of tattoos increased the risk of lymphoma by 163%. Oddly, greater tattoo surface area did not increase risk, with the highest lymphoma risk among people with tattoos smaller than the size of a deck of cards.

    These findings point to potential links between tattoos and an increased risk of lymphoma. The tattooing process involves injecting ink into the skin through repeated punctures, breaching the skin’s protective barrier and triggering an immune response. As the ink enters the body, immune cells called macrophages attempt to engulf and isolate the foreign substance, driving the movement of pigment to nearby lymph nodes. Lasering tattoo ink induces the formation of toxic, carcinogenic substances that can persist in the body.

    Read more
  • Aging isn't linear—it may occur in two distinct bursts in our mid-40s and again around age 60. www.nature.com
    Aging Metabolism Immune System Cardiovascular

    We often think of aging as a steady, downhill slope, but a new study suggests aging happens in two distinct bursts—in our mid-40s and again around age 60—when massive shifts in crucial molecules involved in metabolism and other critical processes occur. These shifts may explain why our disease risk and other hallmarks of aging tend to spike at these pivotal times in our lives.

    The study involved 108 adults aged 25 to 75 years living in the U.S. Researchers assessed changes in 135,000 molecular markers in the participants' blood, feces, and bodily fluids for up to seven years, yielding more than 246 billion data points.

    They found that molecular changes occurred in two massive bursts rather than gradually, with changes in cardiovascular health, lipids, and alcohol metabolism appearing around 44 years of age, followed by shifts in crucial biological processes such as immune regulation and carbohydrate metabolism around 60 years.

    These findings suggest that the progression of aging and related diseases is marked by distinct phases at specific ages. Some lifestyle behaviors can delay the changes that drive aging. Learn more about these powerful habits in this episode featuring Dr. Rhonda Patrick.

    Read more
  • Shorter-chain PFAS alternatives, found in common household products, readily penetrate human skin, potentially increasing the health risks associated with these "forever chemicals." www.sciencedaily.com
    Cancer Immune System Pollution Environment Skin

    Perfluoroalkyl substances, or PFAS, are synthetic compounds found in food packaging, household products, and plastic bottles. These “forever chemicals” persist in the body for indefinite periods, posing significant health risks such as cancer, liver damage, and immune system dysfunction. To address these concerns, chemical companies have introduced shorter-chain PFAS alternatives, which break down more quickly in the environment. However, a recent study found that these alternatives readily penetrate the skin, potentially increasing the health risks associated with PFAS exposure.

    Researchers designed a three-dimensional model that mimicked the qualities of human skin. They applied various PFAS to the model skin, including perfluoroalkyl carboxylic acids (used on/in non-stick cookware, water and stain repellents, and food packaging) and perfluoroalkane sulfonic acids (used on/in carpets, clothing, paper products, and cleaning agents) and assessed whether the compounds were absorbed (consequently taken up into the bloodstream), unabsorbed, or retained within skin tissue.

    The researchers found that the skin absorbed as much as 58.9% of short-chain PFAS, and the absorption rate decreased as the carbon chain length increased. Interestingly, they found that large quantities of longer-chain PFAS (as much as 68.3%) were retained in the skin instead of being absorbed.

    These findings suggest that PFAS, especially shorter-chain forms, readily penetrate human skin and can gain access to the bloodstream. They also underscore the potential health risks of PFAS exposure and the need for further research and regulation.

    Read more
  • Sleep boosts adaptive immune function via the release of hormones that stimulate T-cell migration. www.sciencedirect.com
    Sleep Immune System

    Sleep has profound effects on immune function, driving T-cell migration to lymph nodes – the primary site of adaptive immunity initiation. However, scientists don’t fully understand the mechanisms that underlie links between sleep and immunity. A recent study found that immune-modulating hormones released during sleep mediate T-cell migration.

    The study involved 14 healthy adults with normal sleep patterns. Participants experienced two conditions: 24 hours that included a normal night’s sleep or 24 hours of wakefulness (sleep deprivation). Researchers measured their T-cell numbers, T-cell migration, and hormone levels at various intervals throughout the 24-hour sessions.

    They found that sleep (but not sleep deprivation) increased the spontaneous migration of several T-cell populations toward CCL9, a protein involved in T-cell homing toward lymph nodes. Growth hormone and prolactin (hormones produced in the pituitary gland) mediated these effects. Interestingly, heat exposure induces similar hormonal responses, suggesting that sauna use also bolsters immune function.

    The findings from this small study demonstrate that sleep enhances adaptive immune function by promoting the release of immune-modulating hormones. Learn more about the effects of sleep on immunity in this episode featuring Dr. Roger Seheult.

    Read more
  • Fish oils in intravenous nutrition reduce infection risk by 57 percent and septic risk by 78 percent while shortening hospital stays. www.sciencedirect.com
    Nutrition Omega-3 Inflammation Immune System

    Parenteral nutrition is a method of delivering essential nutrients intravenously when a person is unable to receive nutrition via the digestive system. The solutions used in parenteral nutrition typically include a balanced mix of macro- and micronutrients to support health and promote recovery. A recent review found that parenteral nutrition solutions containing fish oils reduced the risk of infection and sepsis and shortened hospital stays in patients receiving parenteral nutrition.

    Researchers reviewed the findings of 47 randomized controlled trials investigating the effects of parenteral nutrition containing intravenous lipid (fat) emulsions on clinical outcomes in more than 3,600 hospitalized patients. The various emulsions contained one of several lipid types: fish oil, olive oil, medium-chain triglycerides (MCTs), soybean oil, or a combination of MCTs and soybean oil.

    They found that patients who received fish oil were 57 percent less likely to develop an infection than those receiving soybean oil. Similarly, the risk of infection decreased by 41 percent for MCTs/soybean oils and 44 percent for olive oils, compared to soybean oils. Furthermore, the likelihood of sepsis was 78 percent lower with fish oils than soybean oils. Hospital stays decreased by roughly two days among patients receiving fish oils.

    These findings suggest that including fish oil-based lipid emulsions in parenteral nutrition improves outcomes in hospitalized patients. Fish oils are rich in omega-3 fatty acids, which exert potent anti-inflammatory and immunomodulatory properties. Byproducts of omega-3 metabolism called specialized pro-resolving mediators (SPMs) have distinct roles in promoting the resolution of inflammation, restoring homeostasis, and supporting tissue repair. Learn more about SPMs in this episode featuring omega-3 expert Dr. Bill Harris.

    Read more
  • Hyperbaric oxygen therapy reverses aspects of the cellular aging process in older adults, boosting immune cell function. www.sciencedaily.com
    Aging Telomeres DNA Damage Immune System Senescence

    Hyperbaric oxygen therapy involves exposure to oxygen at up to three times the normal pressure, increasing the amount of oxygen the blood can carry. A 2020 study found that hyperbaric oxygen therapy prevented telomere shortening and cellular senescence – hallmarks of cellular aging – in older adults, effectively reversing the aging process.

    The study involved 35 older adults who underwent 60 hyperbaric oxygen therapy treatments over three months. Using blood samples the participants provided before, during, and after the intervention, researchers assessed the participants' immune cell telomere length and senescence.

    They noted a 20 percent or greater increase in T helper, T cytotoxic, natural killer, and B cell telomere length following the hyperbaric treatments. B cell telomeres showed the greatest change, increasing as much as 52 percent post-treatment. B cells facilitate adaptive immunity – producing antibodies against bacterial, viral, and toxic exposures. The number of senescent T helper cells decreased by roughly 37 percent; senescent T cytotoxic cells decreased by 11 percent.

    Telomeres are short, repetitive sequences of DNA located on the ends of chromosomes. They form a protective “cap” – a sort of disposable buffer that gradually shortens with age – that prevents chromosomes from losing genes or sticking to other chromosomes during cell division. When the telomeres on a cell’s chromosomes get too short, the cell stops dividing or dies. Learn more about telomeres in this episode featuring Dr. Elisa Epel.

    Cellular senescence is the condition or process of deterioration that occurs with age. Cells that acquire enough damage can become senescent, rendering them metabolically inactive and unable to replicate. Senescent cells often release proinflammatory cytokines, driving the deterioration of neighboring healthy cells. Learn more about cellular senescence in this episode featuring Dr. Judith Campisi.

    These findings suggest that hyperbaric oxygen therapy reverses some of the effects of aging in immune cells. However, this study was small and had no control group. Future research with larger groups may shed more light on the effectiveness of hyperbaric oxygen in slowing or reversing cellular aging.

    Read more
  • Exercise reduces inflammation and enhances immune surveillance in people with Lynch syndrome, highlighting its cancer prevention potential. www.medscape.com
    Exercise Cancer Inflammation Immune System

    Lynch syndrome is an inherited condition linked to increased risks of colorectal and endometrial cancers. While exercise is known to curb the risk of many types of cancer, scientists don’t fully understand its effects on Lynch syndrome. A recent study found that regular exercise reduced inflammation and boosted immune surveillance in people with Lynch syndrome.

    The study involved 21 people with Lynch syndrome. About half of the participants engaged in a 12-month cycling program (three sessions per week, 45 minutes per session), while the others received standard care and a single exercise counseling session. Researchers assessed the participants' cardiorespiratory fitness and measured gene expression in colorectal tissue before and after the intervention.

    They found that participants' oxygen consumption increased and colon and blood inflammatory markers decreased in those who exercised but not in those who received standard care. Gene expression analysis revealed heightened levels of natural killer and CD8 T cells in those who exercised.

    Natural killer (NK) cells and CD8 T cells play critical roles in the immune system’s defense against cancer. They are crucial components of the body’s immunosurveillance mechanism, responsible for identifying and eliminating potentially cancerous cells.

    These findings underscore exercise’s potential to intercept cancer in Lynch syndrome and shed light on its immunological effects in high-risk people. Learn about the differential effects of exercise intensity and duration on the body’s immune response in this live Q&A featuring Dr. Rhonda Patrick.

    Read more
  • Immune cell depletion promotes depression-like behavior, suggesting a role for regulatory T cells in mood stabilization. neurosciencenews.com
    Depression Immune System Anxiety

    Regulatory T-cells, or Tregs, are white blood cells that modulate the body’s immune response. A growing body of evidence points to the role of immune activation in mood disorders, such as anxiety and depression. A new study in mice shows that Foxp3, a transcription factor, influences Treg expression and activity, ultimately influencing mood.

    Researchers depleted the Foxp3-expressing cells in mice and assessed the animals' behavior. They found that Foxp3 depletion caused temporary anxiety and depression-like behaviors due to the activation of inflammasomes, multi-protein complexes that drive the body’s inflammatory response.

    Then, the researchers restored Foxp3-expressing cells in the mice and found that the anxiety and depression-like behaviors improved. They also noted changes in the innate immune system, including increased activity of caspase-1 (a protein that initiates the immune response) and release of interleukin-1β (a pro-inflammatory cytokine) in the brain.

    These findings suggest that Foxp3 plays a causal role in regulating the immune response, which, in turn, can affect the brain’s innate immune system. They also highlight potential mechanisms that may contribute to anxiety and depression. However, this research was conducted in mice, and extrapolating these findings to humans requires further investigation. Learn about some of the underlying mechanisms that drive depression in this short video.

    Read more
  • Ovarian cancer tumors, even at advanced stages, may be effectively targeted and eliminated by CAR-T immune therapies, a new study in mice suggests. www.sciencedaily.com
    Cancer Genetic Engineering Immune System

    CAR-T, or chimeric antigen receptor T-cell therapy, is an immunotherapy approach that involves genetically modifying a person’s own T cells so they can recognize and target specific proteins on cancer cell surfaces, enhancing the immune system’s capacity to seek out and destroy malignant cells. CAR-T therapies have been successful against blood cancers, such as leukemia, lymphoma, or myeloma, but have largely failed with solid tumors. Now, a new study in mice demonstrates that CAR-T is effective against ovarian cancer, nearly doubling survival time.

    Researchers identified a unique carbohydrate present only on the surface of solid tumor cells, not healthy ones, and engineered CARs with a strong affinity for the carbohydrate. Then, they delivered the CAR-T therapy via intravenous injection to mice with ovarian cancer. Because ovarian cancer treatments delivered directly into the abdominal area are particularly effective, they also administered the CAR-T therapy into the animals' abdomens.

    They found that the CAR-equipped T cells effectively located and eliminated the cancer cells, promoting tumor shrinkage or elimination with just one dose. The genetically engineered cells maintained their effectiveness for several months, with no evidence of toxicity or adverse effects. Intravenous injection of CAR-T cells increased survival to 145 days, but direct delivery into the animals' abdomens extended survival to 270 days.

    These findings demonstrate that modified CAR-T cells show promise as a potential treatment for ovarian cancer and other solid tumors. Future studies are needed to assess the treatment’s effectiveness in humans. Learn more about genetic engineering in this episode featuring Dr. George Church.

    Read more
  • The immune system, recognized for its role in depression, now understood to shape allergen avoidance behavior. www.sciencedaily.com
    Gut Immune System Behavior Allergies

    The immune system plays a critical role in protecting human health. However, a recent study in mice shows that the immune system may influence behavior, too. Mice exposed to allergens – substances that trigger allergies – avoided those substances.

    Researchers studied two groups of mice: one that was predisposed to egg allergy and one that was not. They exposed the two groups to water that contained ovalbumin, a protein in eggs that triggers allergic reactions.

    They found that regions of the predisposed animals' brains that respond to unpleasant stimuli became active when they ingested allergens, causing them to avoid the ovalbumin-containing water. The mechanisms driving this behavior involved activation of IgE antibodies and mast cells (essential immune system components), which, in turn, triggered the activity of key immune-related molecules – cysteinyl leukotrienes and growth and differentiation factor-15 (GDF-15). Interestingly, the animals' avoidance behavior occurred before allergy-associated gut inflammation manifested.

    Cysteinyl leukotrienes are pro-inflammatory lipid mediators produced by various immune cells, including mast cells, eosinophils, basophils, and macrophages. GDF-15 is a cytokine that increases in response to stress, infection, and inflammation. It increases in aging, suppressing immune responses.

    These findings suggest that the immune system can shape behavior in response to allergens in mice, potentially protecting against harmful exposures. The immune system also influences behavior by inducing depressive symptoms during periods of acute or, alternatively, chronic inflammation. Learn more in this clip featuring Dr. Charles Raison.

    Read more
  • Regular exercise reprograms bone marrow macrophages, inducing lasting mitochondrial changes that accumulate, driving a tempered inflammatory response. www.sciencedaily.com
    Exercise Inflammation Immune System Mitochondria

    Although inflammation is a critical component of the body’s immune response, excess inflammation drives many chronic diseases, such as autoimmune disorders, cardiovascular diseases, diabetes, and cancer. A new study in mice shows that regular exercise reprograms macrophages, altering how they sense and respond to pathogens and reducing inflammation.

    Macrophages are immune cells that participate in pathogen elimination via phagocytosis. Distinguished by their polarization, “M1” macrophages exhibit a proinflammatory phenotype, while “M2” macrophages exhibit an anti-inflammatory phenotype. A high M1 to M2 ratio indicates inflammation and a chronic disease state.

    Researchers collected macrophages from the bone marrow of two groups of mice – one that had exercised regularly for eight weeks and one that had been sedentary. Then they exposed the macrophages to lipopolysaccharide (a bacterial toxin that induces an acute inflammatory reaction) and assessed the cells' responses.

    They found that macrophages from the exercised mice exhibited decreased activation of NF-κB, the primary transcription factor of M1 macrophages. The macrophages also demonstrated reduced expression of inflammation-related genes, increased expression of M2 macrophage-associated genes, and improved mitochondrial function.

    These findings suggest that regular exercise modulates macrophages' responses to inflammation by enhancing their respiratory capacity and altering gene expression, with potential implications for preventing or treating inflammatory diseases. Read more about the benefits of exercise in our overview article.

    Read more
  • The unique balance of gut viruses, termed the virome, may hold the secret to centenarians' longevity, new research proposes. healthsciences.ku.dk
    Aging Microbiome Immune System Virus

    The gut virome – the collection of viruses inhabiting the gut – plays a crucial role in shaping the immune system and defending against infections throughout the lifespan. A new study shows that centenarians' viromes differ from those of younger people, potentially contributing to their longevity.

    Researchers examined the gut viromes of centenarians and compared them with those of younger people. Then they analyzed the viruses' auxiliary metabolic gene activity. Auxiliary metabolic genes are found in bacteriophages – viruses that infect bacteria. They help viruses manipulate their host cells' metabolism to facilitate viral replication.

    They found that the centenarians exhibited more diverse viromes than younger people. In addition, the centenarians' viromes demonstrated increased lytic activity, indicating that their viromes were more active in infecting and destroying bacterial cells. Finally, they found that the centenarians' gut viruses possessed an abundance of auxiliary metabolic genes involved in sulfate metabolism, the byproducts of which promote gut integrity and pathogen resistance.

    These findings suggest that centenarians' viromes differ markedly from those of younger people in terms of makeup and activity, potentially contributing to centenarians' healthspan and longevity. Learn more about the role gut microbial populations play in human health in this episode featuring Dr. Eran Elinav.

    Read more
  • Swabbing C-section newborns with their mothers' vaginal fluid promotes healthier neurodevelopment at 3 and 6 months, bridging the gap to vaginally del www.newscientist.com
    Microbiome Immune System Pregnancy Development

    Infants born by cesarean section have different microbial communities in and on their bodies than those born vaginally, potentially increasing their risk of developing certain diseases, such as asthma and obesity. But a new study shows that vaginal microbiota transfer – exposing newborns to fluids from their mother’s vagina – may rectify these differences.

    The study involved 68 infants born by cesarean section. Researchers swabbed the infants' skin with sterile gauze soaked in either the mother’s vaginal fluids or saline immediately after birth. They assessed the infants' neurodevelopment at three and six months of age and analyzed the microbial makeup of the infants' guts.

    They found that infants who received vaginal microbiota transfer scored higher on neurodevelopment assessments than those who received saline. They also had healthier, more mature gut microbiomes – comparable to infants born vaginally.

    These findings suggest that exposing infants born via cesarean section to their mother’s vaginal fluids promotes appropriate neurodevelopment and corrects alterations in gut microbial populations. Learn more about the importance of establishing a healthy microbiome early in life in this clip featuring Dr. Eran Elinav.

    Read more
  • Microglial dormancy in depression challenges conventional understanding centered on inflammation, but highlights the immune cell's crucial role in neu medicalxpress.com
    Brain Inflammation Depression Immune System

    Chronic inflammation is a dominant feature in people who have depression, suggesting that an overactive immune response drives the disease’s symptoms. But a new study demonstrates something counterintuitive in spite of that: Immune cells in the brain called microglia are less active in people with depression, impairing their ability to clear damaged neuronal connections, undermining neurotrophic support, and driving the disease.

    Researchers studied gene expression in the microglia of brain tissues collected during autopsies of 13 people with depression and 10 healthy people. They also examined gene expression of neuronal factors that regulate microglial function.

    They found that the expression of genes in the microglia of people with depression was markedly lower than that of healthy people, especially genes involved in immune responses and phagocytosis (which facilitates the clearance of damaged cells). In addition, the expression of factors involved in immune suppression (CD200 and CD47) was higher.

    These findings suggest that people with depression have a distinct disease-associated microglia gene expression profile that impairs microglia activity. Microglia play critical roles in the development, homeostasis, and diseases of the central nervous system and contribute to neuronal plasticity in the healthy brain. Microglial changes are common features of many neuropsychiatric disorders, including schizophrenia, autism spectrum disorder, and bipolar disorder. Learn more about microglia suppression in depression in this clip featuring Dr. Charles Raison.

    Read more
  • Eating broccoli may safeguard the gut by increasing the number of goblet and Paneth cells. www.sciencedaily.com
    Gut Diet Inflammation Immune System Sulforaphane

    The list of health attributes of broccoli includes anticancer, antioxidant, and anti-diabetes effects, as well as many others. Now a new study in mice shows that eating broccoli protects the gut. Molecules in broccoli interact with proteins present in the small intestine, increasing the number of cells involved in safeguarding the gut.

    Researchers fed one group of mice a diet containing 15 percent freeze-dried broccoli – roughly equivalent to 3.5 cups of fresh broccoli in the human diet. They fed another group their typical food, which included no broccoli. Then they examined the animals' small intestines to assess the effects of broccoli consumption on the gut.

    They found that molecules in the broccoli – likely phytochemicals, microbiota, or byproducts of metabolism – bound with specific proteins in the gut called aryl hydrocarbon receptors. Subsequently, the number of goblet and Paneth cells in the animals' guts increased. Goblet cells produce mucus, which protects and lubricates the gut to facilitate the passage of food. Paneth cells produce antimicrobial peptides and immune factors that regulate the gut microbial composition.

    These findings suggest that broccoli consumption protects the gut via interaction with the aryl hydrocarbon receptor. Broccoli is a rich source of phytochemicals, including sulforaphane, an isothiocyanate compound with potent antioxidant, anticancer, and anti-inflammatory properties. Learn more about sulforaphane in this episode featuring Dr. Jed Fahey.

    Read more
  • Blocking the body's antiviral immune response holds promise for Alzheimer's disease prevention. medicalxpress.com
    Alzheimer's Aging Immune System Virus

    The immune system plays important, and sometimes surprising, roles in brain health. A new study in mice found that blocking components of the antiviral immune response may make the brain more resilient to the effects of abnormal tau – potentially preventing Alzheimer’s disease and other forms of dementia.

    Tau is a protein found in the brain. Abnormal tau can form aggregates called tau tangles – one of the defining characteristics of Alzheimer’s disease – activating antiviral response pathways and interfering with normal brain function and cognition.

    Researchers studied the effects of exposure to abnormal tau on microglia, the brain’s resident immune cells. They found that when microglia were exposed to abnormal tau, the mitochondria became “leaky,” releasing their DNA into the cellular fluid. The immune system inappropriately interpreted the leaked DNA as a viral attack, triggering an immune response that promoted the release of type-I interferon, a cytokine that drives the antiviral immune response. Interrupting the pathways involved in this response restored normal brain function.

    These findings suggest that suppressing the inappropriate immune response to abnormal tau exposure could provide a means to prevent or treat the tau-associated pathologies common in Alzheimer’s disease and dementia. Learn about other strategies to reduce the risk of Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

    Read more
  • Experimental vaccine may prevent peanut allergy. newatlas.com
    Immune System Vaccine Allergies

    A recent study demonstrated that an experimental mRNA-based vaccine prevented peanut allergy in mice. The vaccine effectively induced peanut protein tolerance, reducing or preventing symptoms of allergy.

    Researchers developed a lipid nanoparticle vaccine that delivered mRNA-encoded peanut allergen and administered it to mice that are prone to peanut allergy. Then they exposed the mice to peanut protein and assessed their immune response.

    They found that the mRNA vaccine induced the production of T regulatory cells, a specialized type of T cells that suppress the body’s immune response. The vaccine also reduced cytokine production, antibody synthesis, and mast cell release – indicators of an allergic response.

    Peanut allergy is one of the most common food allergies, affecting approximately 2 percent of adults and children in the United States. Typically manifesting early in life, symptoms of peanut allergy include rashes, shortness of breath, and life-threatening anaphylaxis.

    mRNA-based vaccines contain the genetic material to encode a single protein that, when injected into the body, induces antibody production against that protein – in this case, a peanut allergen. Because mRNA degrades easily, it must be encapsulated in lipid nanoparticles.

    These findings suggest that an mRNA-based vaccine prevents peanut allergy in mice. Although mRNA-based vaccines have been used in clinical trials for nearly two decades, this study reflects their first use against an allergen. Learn more about mRNA vaccines in this clip featuring Dr. Roger Seheult.

    Read more
  • Higher omega-3 status may confer protection against COVID-19, according to a new study. www.ncbi.nlm.nih.gov
    Omega-3 Inflammation Immune System COVID-19

    Omega-3 fatty acids may protect against COVID-19, a new study shows. People with higher levels of omega-3s in their red blood cells were less likely to contract COVID-19 or require hospitalization if infected.

    Researchers calculated the concentrations of docosahexaenoic acid (DHA), a type of omega-3 derived from fatty fish, in the blood of more than 110,000 people enrolled in the UK Biobank study. They also calculated the participants' Omega-3 Index – a measure of total omega-3 fatty acid concentrations in red blood cells. They reviewed the participants' medical records to determine if they had ever contracted COVID-19 and, if so, the severity and outcome of their disease.

    They found that people with the highest Omega-3 Indices (8 percent) were less likely to contract COVID-19 or have a severe outcome than those with the lowest Indices (3.5 percent). Those with the highest DHA levels were 21 percent less likely to test positive for COVID-19 and 26 percent less likely to be hospitalized due to COVID-19 infection.

    In silico (computer modeling) experiments demonstrate that one of the mechanisms driving omega-3s' protective effects in the setting of COVID-19 may be related to their capacity to prevent the spike protein, the primary antigenic component of SARS-CoV-2, from binding to cellular receptors that allow the virus to enter cells. Other evidence points to the anti-inflammatory properties of omega-3s, which may reduce host inflammatory response and disease severity.

    These findings suggest that omega-3s confer protection against COVID-19. Listen to former FMF guest and omega-3 expert Dr. Bill Harris elaborate on this study.

    Read more
  • Mild intermittent fasting can have a surprisingly negative effect on immunity: skipping breakfast led to a 90% drop in white blood cell count. www.sciencetimes.com
    Diet Fasting Immune System

    Skipping breakfast may impair immune function.

    Skipping breakfast adversely affects immune health, a new study in mice shows. Mice that skipped breakfast experienced a 90 percent drop in white blood cell numbers and demonstrated impaired immune function.

    Researchers investigated the effects of fasting on immune health in two groups of mice. One group of mice ate breakfast upon waking, while the other group fasted, skipping breakfast. The researchers measured white blood cell numbers immediately after both groups of mice woke up and at four and eight hours after waking. Then they infected the mice with a type of bacteria that commonly causes pneumonia to see how their immune systems responded.

    They found that after just four hours, the white blood cell numbers in the blood of fasting mice decreased by 90 percent, having accumulated in the bone marrow. Upon refeeding, the number of white blood cells in circulation increased markedly, and most of these cells were older and exhibited pro-inflammatory characteristics. After exposure to the pneumonia-causing bacteria, the mice that fasted were more likely to die (and died sooner) than the mice that didn’t fast.

    These findings suggest that skipping breakfast during fasting impairs immunity. They also align with evidence that an earlier eating window when practicing time-restricted eating (which involves a long overnight fast) is more beneficial](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634676/) than a later one. Learn more about time-restricted eating in this episode featuring Dr. Satchin Panda.](https://www.foundmyfitness.com/episodes/satchin-panda-3)

    Read more
  • Babies breastfed for at least three months are less likely to get sick. bmcpublichealth.biomedcentral.com
    Immune System Development Breast Milk

    Breastfeeding protects infants from many common illnesses, a new study has found. Babies breastfed for at least three months were less likely to spend time in the hospital or develop asthma, colds, ear infections, or other common conditions.

    Researchers tracked the health and breastfeeding histories of nearly 4,000 children living in Ireland. They compared the rates of hospitalization and illnesses of babies fed breast milk exclusively for 90 days or more to those who never breastfed.

    They found that babies breastfed for 90 days or more were less likely to develop chest infections, common colds, ear infections, asthma, respiratory problems, eczema, skin allergies or problems, vomiting, and colic, compared to those who never breastfed. Breastfed babies were also less likely to require medical treatment or be hospitalized.

    These findings support the practice of breastfeeding for optimal infant health. They also underscore the benefits of breast milk, even for infants born in a developed nation.

    Breast milk is a complex, dynamic fluid that contains nutritional and non-nutritional components that positively influence an infant’s health and development. These components work together synergistically to supply a compensatory immune “system” that includes antimicrobial and anti-inflammatory agents, immunomodulatory factors, leukocytes, and others. Learn more about breast milk and breastfeeding in our overview article.

    Read more
  • Early-life obesity increases the risk of macular degeneration later in life. www.sciencedaily.com
    Obesity Metabolism Inflammation Immune System Eyes

    Obesity in early life induces changes in immune cells that may increase the risk of macular degeneration later in life, a study in mice has found. These changes linger even after weight loss and the restoration of normal metabolism.

    Researchers fed mice a diet that promoted weight gain early in life. Then they studied the effects of having excess body fat on the animals' adipose tissue macrophages – a type of immune cell found in fat. Later, they put the mice on a diet that promoted weight loss.

    They found that having excess body fat induced epigenetic changes in the macrophages that, in turn, induced an inflammatory response. This pro-inflammatory response persisted even after the mice lost weight. They also found that the macrophages could migrate from the fatty tissue to other parts of the body, including the eyes, where they could contribute to the onset of macular degeneration.

    Macular degeneration is the leading cause of blindness worldwide. Having excess body fat is the second leading risk factor for macular degeneration. In fact, a person’s risk of developing macular degeneration increases by 75 percent with each 0.1 increase in their waist-to-hip ratio – a measure of abdominal obesity.

    Read more
  • Levels of PFAS, a group of synthetic chemicals, were 278 times higher in freshwater fish across the U.S. than in commercially-sold fish. (2023) doi.org
    Cancer Diet Cholesterol Immune System Development Environment

    From the publication:

    Per- and polyfluoroalkyl substances (PFAS), previously referred to as “perfluorinated compounds”, are a class of manufactured chemicals that have been detected in nearly all sampling of geographic locations and environmental matrices worldwide, including sites that had no nearby manufacture or use of PFAS. PFAS are used in hundreds of industrial and consumer products including food packaging and waterproof/stain resistant fabrics. Their strong carbon-fluorine bonds provide both hydrophobic and oleophobic properties, which make these chemicals extremely persistent in the environment. The class of PFAS includes tens of thousands of potential environmental contaminants including over one thousand chemicals previously or currently approved for use in the U.S..

    For PFAS measured at concentrations already found in the general population, exposure may suppress the immune system. Additionally, exposure to PFAS, with most studies on PFOA and PFOS, has been associated with many health harms, including an increased risk of cancer, high cholesterol, thyroid disease, and reproductive and developmental harms.

    The median level of total targeted PFAS in fish fillets from rivers and streams across the United States was 9,500 ng/kg, with a median level of 11,800 ng/kg in the Great Lakes. PFOS was the largest contributor to total PFAS levels, averaging 74% of the total. The median levels of total detected PFAS in freshwater fish across the United States were 278 times higher than levels in commercially relevant fish tested by the U.S. Food and Drug Administration in 2019–2022. Exposure assessment suggests that a single serving of freshwater fish per year with the median level of PFAS as detected by the U.S. EPA monitoring programs translates into a significant increase of PFOS levels in blood serum.

    Additional information:

    In June 2018, the Agency for Toxic Substances and Disease Registry (ATSDR) released a draft Toxicological Profile that derived minimal risk levels (MRLs), which are similar to RfDs, for intermediate duration exposure (15–364 days) of four PFAS routinely measured in NHANES [28]. The MRL [minimal risk levels] values for PFOA (3 ng/kg/day) and PFOS (2 ng/kg/day) are 6.7 and 10 times lower than the RfDs EPA used to develop its 2016 HAs and similar to those developed by New Jersey, though they are based on different studies and endpoints. View full publication

    Read more
  • Gene-edited tumor cells used as a "tumor-killing" cancer vaccine in a new approach to treating glioblastoma. medicalxpress.com
    Cancer Immune System Vaccine

    An experimental vaccine killed brain cancer cells and prevented them from returning, a new study in mice has found. The mice lived longer and had improved anti-cancer immunity.

    Using CRISPR-Cas9, a powerful gene editing tool, researchers modified living tumor cells so that they would secrete interferon-beta and granulocyte-macrophage colony-stimulating factor – two potent immunomodulatory and anti-tumor agents. Then they incorporated a “kill switch” in the modified cells that would prevent secondary tumor initiation.

    They found that the modified tumor cells killed glioblastoma tumor cells by inducing apoptosis (cell death) and turning off the activity of cancer growth factors. The modified cells also turned on normal anti-cancer immune cell activities and signaling, improving the animals' survival and promoting their long-term immunity.

    This study in mice provides proof of concept for the use of genetically modified living tumor cells as anti-tumor agents and paves the way for their future use in humans. Learn more about therapeutic uses of gene editing in this episode featuring Dr. George Church.

    Read more
  • Tumor cell-independent estrogen signaling may drive disease progression by mobilizing immune cells associated with tumor treatment resistance. (2016) www.sciencedaily.com
    Cancer Hormones Breast Cancer Immune System Estrogen

    From the article:

    Conejo-Garcia and colleagues found that estrogen signaling is closely linked to both the accumulation and activity of myeloid-derived suppressor cells (MDSCs), a set of immune cells associated with tumors treatment resistance. Estrogen enables immunosuppression in a two-pronged approach involving MDSCs. First, the estrogen drives the mobilization of MSDCs. Then, at the same time, it makes a subset of the MDSCs more immunosuppressive in vivo. Estrogen supplementation accelerated the growth of multiple models estrogen-insensitive tumors in immunocompetent animals, while ablating estrogen production by resecting the ovaries boosted anti-tumor immunity and delayed malignant progression. Importantly, differences in tumor progression disappeared in immunodeficient mice, demonstrating that estrogen-mediated acceleration of tumor growth depends on dampening protective anti-tumor immunity.

    They also demonstrated how ERα is responsible for enhancing the activity of multiple pathways that are already associated with cancer development. This estrogen receptor activated the STAT3 pathway, which has already been linked to cancer cell survival and the expansion of MDSCs in cancer-bearing hosts. It was also able to activate this pathway by enhancing the activity of JAK2 and SRC, two proteins linked to cancer development and immune response.

    These cancer pathways are activated in a variety of inflammatory cancers in non-tumor cells, such as breast cancer, ovarian cancer, and melanoma. Since estrogen is present not just pre-menopausal women but men and post-menopausal women as well, the authors propose that investigating anti-estrogen therapeutic strategies could lead to new treatments for a variety of cancers. This strategy could halt the mobilization of MDSCs and tumor initiation.

    View full publication

    Read more
  • Estrogen may exert inhibitory effects on immune cells, leading to reduced vascular inflammation and protection against cardiovascular disease. (2011) www.sciencedaily.com
    Hormones Heart Disease Immune System Estrogen Cardiovascular

    From the article:

    The results could help explain why cardiovascular disease rates tend to be higher in men and why they soar in women after the menopause.

    The researchers compared white blood cells from men and pre-menopausal women blood donors. They found that cells from premenopausal women have much higher levels of protein called annexin-A1 on the surface of their white blood cells.

    The scientists also found that annexin-A1 and estrogen levels were strongly linked throughout the menstrual cycle.

    White blood cells play a vital role in protecting the body from infections. When they are activated they stick to the walls of blood vessels. This process normally helps the cells to tackle infection but if it happens too much, it can lead to blood vessel damage, which in turn can lead to cardiovascular disease. However, when annexin-A1 is on the surface of these white blood cells, it prevents them from sticking to the blood vessel wall.

    The new research shows that estrogen can move annexin-A1 from inside the white blood cell, where it is normally stored, to the surface of the cells, thereby preventing the cells from sticking to blood vessel walls and causing vascular damage. This may have important implications in cardiovascular disease.

    View full publication

    Read more
  • Estradiol enhances anti-viral responses in the genital tract of mice infected with herpes simplex virus type 2. (2016) www.sciencedaily.com
    Hormones Immune System Virus Sex Estrogen

    From the article:

    “If this pathway can be verified in women, then we have laid the foundation to address a number of important public health issues, particularly whether some hormonal contraceptives may be better than others for women who are at higher risk of acquiring sexually transmitted infections, such as in Sub-Saharan Africa, where both HIV-1 and HSV-2 infection rates are high.”

    As part of the study, researchers implanted estradiol-releasing pellets into female mice whose ovaries had been removed. The mice then received two rounds of an HSV-2 vaccine, followed by a high dose of the virus.

    The researchers saw that the majority of the mice survived and showed less severe disease symptoms, compared to a control group that was not immunized. Further analysis of the molecular pathways underpinning this defensive mechanism revealed that estradiol primes dendritic cells in the vaginal tract to initiate anti-viral T cell immunity.

    More specifically, the researchers reported an increase in anti-viral activity unique to the vaginal tract and not found in any other mucosal lining of the body.

    View full publication

    Read more
  • High-intensity aerobic exercise may reduce the risk of colds and other upper respiratory infections by nearly half. bjsm.bmj.com
    Exercise Immune System

    People who regularly engage in high-intensity aerobic exercise have nearly half as many upper respiratory infections as sedentary people, a 2010 study found. Those who engage in high-intensity aerobic exercise also experience fewer and less severe upper respiratory symptoms than those who engage in lower-intensity exercise.

    Researchers tracked the number and severity of respiratory infections during the fall and winter of a single year among more than 1,000 adults. The participants, who were between the ages of 18 and 85 years, provided information about the frequency and intensity of their aerobic physical exercise during the 12-week period.

    The researchers found that those who engaged in aerobic physical exercise five or more times per week reported 43 percent fewer upper respiratory infections than those who were sedentary. Those who engaged in high-intensity exercise reported 46 percent fewer infections than those who engaged in low-intensity exercise. Upper respiratory symptoms were 32 to 41 percent less severe among those who engaged in high-intensity exercise compared with those who engaged in low-intensity exercise.

    These findings suggest that regular aerobic exercise – especially high-intensity exercise – protects against upper respiratory infections. Other research suggests that during aerobic exercise, profound molecular changes occur that enhance the production of beneficial cytokines and other factors that support immune health. Learn more about the effects of exercise on immunity in this clip featuring Dr. Michael Snyder.

    Read more
  • Estrogen may contribute to T cell–mediated autoimmune inflammation by promoting T cell activation and proliferation, mouse study suggests. ( 2018) www.sciencedaily.com
    Hormones Immune System Estrogen Autoimmunity

    From the article:

    Estrogen hormone shows its action on cells mostly through (ERα). Researchers from Turku generated mice with ERα protein specifically deleted in T cells.

    “The eureka moment of our research is that in a mouse model of human inflammatory bowel disease, transfer of naive T helper cells from ERα [estrogen receptor alpha] deficient mice did not succumb to colitis, unlike transfer from their counterparts,” Docent Zhi Chen tells.

    “Furthermore, using cutting-edge technique RNA sequencing approach combined with in vitro and in vivo experiments, we discovered that ERα regulates multiple aspects of T cell function, including T cell activation, proliferation and survival,” Chen adds.

    Regulatory T cells are group of T cells that help in preventing autoimmune diseases. The researchers found that ERα influences the function and differentiation of regulatory T cells.

    View full publication

    Read more
  • High testosterone may indirectly weaken immune response to vaccination in men by interacting with related genes. (2013) www.sciencedaily.com
    Hormones Immune System Vaccine Testosterone

    From the article:

    In the study, women had a generally stronger antibody response to the vaccine than men. But the average response mounted by men with relatively low testosterone levels was more or less equivalent to that of women.

    […]

    Women are known to have, on average, higher blood levels of signaling proteins that immune cells pass back and fort to jump-start inflammation, a key component of immune-system activation. Furthermore, previous research in animals and in cell-culture experiments has established that testosterone has anti-inflammatory properties, suggesting a possible interaction between the male sex hormone and immune response.

    […]

    However, the new study found no connection between circulating levels of pro-inflammatory proteins and responsiveness to the flu vaccine. Nor does testosterone appear to directly chill immune response; rather, it seems to interact with a set of genes in a way that damps that response, said the study’s senior author, Mark Davis, PhD, professor of microbiology and immunology and director of Stanford’s Institute for Immunity, Transplantation and Infection.

    […]

    Men are prone to suffer wounds from their competitive encounters, not to mention from their traditional roles in hunting, defending kin and hauling things around, increasing their infection risk.

    While it’s good to have a decent immune response to pathogens, an overreaction to them – as occurs in highly virulent influenza strains, SARS, dengue and many other diseases – can be more damaging than the pathogen itself. Women, with their robust immune responses, are twice as susceptible as men to death from the systemic inflammatory overdrive called sepsis. So perhaps, Davis suggests, having a somewhat weakened (but not too weak) immune system can prove more lifesaving than life-threatening for a dominant male in the prime of life.

    View full publication

    Read more
  • COVID-19 may deplete testosterone, helping to explain male patients' poorer prognosis. (2020) www.sciencedaily.com
    Hormones Immune System Testosterone COVID-19

    From the article:

    “Testosterone is associated with the immune system of respiratory organs, and low levels of testosterone might increase the risk of respiratory infections. Low testosterone is also associated with infection-related hospitalisation and all-cause mortality in male in ICU patients, so testosterone treatment may also have benefits beyond improving outcomes for COVID-19,” Professor Çayan explains.

    “In our study, the mean total testosterone decreased, as the severity of the COVID-19 increased. The mean total testosterone level was significantly lower in the ICU group than in the asymptomatic group. In addition, the mean total testosterone level was significantly lower in the ICU group than in the Intermediate Care Unit group. The mean serum follicle stimulating hormone level was significantly higher in the ICU group than in the asymptomatic group.

    “We found, Hypogonadism – a condition in which the body doesn’t produce enough testosterone -in 113 (51.1%) of the male patients.

    “The patients who died, had significantly lower mean total testosterone than the patients who were alive.

    “However, even 65.2% of the 46 male patients who were asymptomatic had a loss of loss of libido.”

    […]

    In the patients who had pre-COVID-19 serum gonadal hormones test (n: 24), serum total testosterone level significantly decreased from pre-COVID-19 level of 458±198 ng/dl to 315±12 ng/dl at the time of COVID-19 in the patients (p=0.003).

    View full publication

    Read more
  • Amazonian forager-horticulturalists have lower testosterone levels than U.S. men, but show short-term testosterone spikes during competition. (2012) www.sciencedaily.com
    Exercise Hormones Immune System Testosterone

    From the article:

    But new research shows that Tsimane (“chi-MAH-nay”) men have a third less baseline testosterone compared with men living in the United States, where life is less physically demanding. And unlike men in the U.S., the Bolivian foragers-farmers do not show declines in testosterone with age.

    “Maintaining high levels of testosterone compromises the immune system, so it makes sense to keep it low in environments where parasites and pathogens are rampant, as they are where the Tsimane live,” said Ben Trumble, an anthropology graduate student at the University of Washington.

    That men living in the U.S. have greater circulating levels of testosterone represents an “evolutionarily novel spike,” Trumble said. The spike reflects how low levels of pathogens and parasites in the U.S. and other industrialized countries allow men to maintain higher testosterone without risking infection.

    […]

    Despite lower circulating levels of testosterone under normal conditions, the forager-farmers do have something in common with U.S. men: short-term spikes of testosterone during competition.

    Trumble and his co-authors organized a soccer tournament for eight Tsimane teams. The researchers found that Tsimane men had a 30 percent increase in testosterone immediately after a soccer game. An hour after the game, testosterone was still 15 percent higher than under normal conditions. Similar percent increases have been shown in men living in the U.S. or other industrialized nations following sports competitions.

    […]

    “What’s interesting is that in spite of being in a more pathogenic environment, it’s still important to raise testosterone for short-term bursts of energy and competition,” said Michael Gurven, co-author and anthropology professor at the University of California Santa Barbara.

    View full publication

    Read more
  • Testosterone may protect against inflammation by reducing phospholipase D activity in immune cells, cell study suggests. (2011) www.sciencedaily.com
    Hormones Inflammation Immune System Testosterone Cardiovascular

    From the publication:

    “In a series of analyses we have shown that cells from men and women react in a different manner to inflammatory stimuli,” Dr. Carlo Pergola from the Institute of Pharmacy of University Jena explains. Thus, certain immune cells of women produced nearly twice as many pro-inflammatory substances than those of men. Together with colleagues from Tübingen (Germany), Stockholm (Sweden) and Naples (Italy) the Jena researchers pursued the molecular basis for these differences and published their findings in their current study. To this aim, they isolated immune cells of male and female donors and analyzed in test tubes the activity of the enzymes responsible for the production of pro-inflammatory substances. They found that in male cells the enzyme phospholipase D is less active than in the female ones. “Interestingly, the activity of the enzyme is reduced after treatment with testosterone also in the female immune cells“, Dr. Pergola defines a crucial result.

    Based on these findings, the Jena pharmacists concluded that the male sex hormones play a key role in the modulation of the immune response. This would also explain another phenomenon that has been previously noticed, that is, testosterone can protect men from arteriosclerosis.

    View full publication

    Read more
  • Chronic poor sleep activates the immune system and promotes inflammation. rupress.org
    Sleep Inflammation Immune System

    A new study shows that chronic poor sleep increases immune cell numbers and promotes inflammation, but good, consistent sleep helps maintain a healthy balance of white blood cells and supports normal immune function.

    The study involved 14 healthy adults who experienced two six-week sleep protocols – one in which they got sufficient sleep (about 7.5 hours) every night and one in which they got about 6 hours of sleep every night – separated by a six-week break. The investigators measured inflammatory markers in the participants' blood every morning and afternoon of the last two weeks of each protocol.

    They found that when the participants didn’t get enough sleep, their afternoon blood samples had higher levels of immune cells called monocytes and markers of immune activation compared to when they got enough sleep. Poor sleep also induced epigenetic changes in stem cells that produce immune cells, reducing their progeny’s diversity and tipping the balance of immune cell production toward an inflammatory profile.

    Sleep has profound effects on human health. Not getting enough sleep or having poor, fragmented sleep drives an increase in the production of myeloid cells, a type of white blood cell that predominates in aging and activates inflammasomes – drivers of inflammation.

    These findings suggest that sleep preserves healthy immune cell production, thereby reducing inflammation. Learn more about the health benefits of sleep in this episode featuring Dr. Matthew Walker.

    Read more
  • Testosterone protects men from developing allergic asthma by inhibiting a certain type of immune cell, mouse study suggests. (2017) www.sciencedaily.com
    Hormones Immune System Testosterone Allergies Asthma

    From the article:

    “There is a very interesting clinical observation that women are more affected and develop more severe asthma than men, and so we tried to understand why this was happening,” Dr Seillet said.

    “Our research shows that high levels of testosterone in males protect them against the development of allergic asthma. We identified that testosterone is a potent inhibitor of innate lymphoid cells, a newly-described immune cell that has been associated with the initiation of asthma.”

    The research team found that innate lymphoid cells – or ILC2s – ‘sensed’ testosterone and responded by halting production of the cells.

    “Testosterone directly acts on ILC2s by inhibiting their proliferation,” Dr Seillet said. “So in males, you have less ILC2s in the lungs and this directly correlates with the reduced severity of asthma.”

    ILC2s are found in the lungs, skin and other organs. These cells produce inflammatory proteins that can cause lung inflammation and damage in response to common triggers for allergic asthma, such as pollen, dust mites, cigarette smoke and pet hair.

    View full publication

    Read more
  • Immune cells in the brain influence high-order cognitive function but increase the risk of neuropsychiatric disorders. www.science.org
    Brain Immune System

    The dorsolateral prefrontal cortex is a functional region of the brain that mediates complex cognitive functions. It is unique to primates. Findings from a recent study suggest that specialized immune cells called microglia are present in the dorsolateral prefrontal cortex of humans only, setting them apart in terms of cognitive abilities but making them more vulnerable to language and neuropsychiatric disorders.

    Microglia are the brain’s resident immune cells. Their acute activation modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.

    Researchers profiled the expression of genes in more than 600,000 cells found in the dorsolateral prefrontal cortices of four primate groups, including humans, macaques, chimpanzees, and marmosets. They identified 109 cell types that were conserved across the four species and five that were species-specific.

    Of the species-specific cell types, they noted that one type of microglia was only found in humans, while another was found in both humans and chimpanzees. They also found that microglia express a gene called FOXP2, which is involved in language disorders, schizophrenia, and autism.

    These findings suggest that microglia play critical roles in establishing higher-order cognitive function in humans, but they may also increase humans' risk for language and neuropsychiatric disorders.

    Read more
  • Chronic stress can inflame our brain, destroy the connections between our neurons and result in depression. (2019) www.sciencedaily.com
    Brain Immune System

    From the article:

    The complement system, named because it was first found to help the immune system fight invaders, is part of this innate immune response, and Pillai has found elevated levels of C3 – which he calls the hub of all complement activation pathways – in both the brains of people with depression and animal models.

    The complement system also has the important job during development of removing bad connections between neurons, and there is good evidence the same thing happens in a developed brain in problems like major depressive disorder and Alzheimer’s, when losing these important connections, called synapses, is problematic rather than helpful.

    “You have to have a functioning complement system during development,” says Pillai. But he and his research colleagues have put together some of the first evidence that in depression, the complement also is active, causing inflammation and synaptic loss in the prefrontal cortex, an area of the brain important to working memory, personality and executive function. “Under chronic stress you are losing your synapses,” he says.

    C3 is known to play a key role in inflammation in the brain, and microglia, the resident immune cells in the brain, are known to use C3 during brain development to eliminate synapses.

    “We expect that chronic stress increases C3,” Pillai says as he continues to put the complex puzzle together.

    […]

    Their early findings indicate that when NF-kappa B, a transcription factor that regulates both innate and adaptive immunity and is implicated as a key regulator of inflammation in depression, is inhibited, stress-induced increases of C3 in a mouse’s prefrontal cortex are reduced. Depleting microglia appears to do essentially the same thing.

    View full publication

    Read more
  • New study explores infection effect on fetal brain development medicalxpress.com
    Brain Immune System Development

    Maternal infection during pregnancy influences fetal neurodevelopment.

    Maternal immune activation due to infection, allergies, or other exposures during pregnancy switches on the activity of a wide array of inflammatory pathways and proinflammatory molecules. These molecules can cross the blood-brain barrier and the placenta, potentially disrupting fetal neurodevelopment and impairing sensory processing abilities later in life. These impairments are often manifested in neuropsychiatric disorders such as autism or schizophrenia. Findings from a recent study suggest that interleukin-15 modulates the effects of a simulated viral infection during pregnancy.

    Interleukin 15, a cytokine that is found primarily in immune cells, plays important roles in regulation of the antiviral immune response. IL-15 also participates in the development of natural killer cells, a type of immune cell that is present in large numbers in the uterus during early pregnancy and participates in placental development.

    The study investigators injected pregnant normal mice and mice that lacked IL-15 with polyinosinic:polycytidylic (poly I:C), a chemical used in the laboratory setting to simulate a viral infection. Poly I:C interacts with toll-like receptors to elicit an immune response. Other normal and IL-15-deficient mice received saline injections. The investigators tested the animals' offspring in adolescence and adulthood to identify behavioral problems and auditory hypersensitivity. They collected brain tissue samples from a subset of the offspring for examination.

    They found that offspring of IL-15-deficient mice that experienced immune activation during pregnancy were more likely to exhibit behavioral problems and auditory hypersensitivity, suggesting that IL-15 plays roles in brain development. They also noted that exposure to poly I:C and IL-15 deficiency independently altered behavioral manifestations in the mice. However, IL-15 deficiency influenced some of the effects of poly I:C exposure.

    These findings suggest that IL-15 modulates the effects of maternal immune activation during pregnancy, with potential long-lasting effects on offspring behavior. They also underscore the importance of appropriate vaccination before and during pregnancy to minimized immune activation and its potential harms.

    Read more
  • Managing phage therapy to help save lives medicalxpress.com
    Immune System Virus

    Genomic analysis reveals important insights regarding bacteriophage therapy for multidrug resistance bacteria.

    In recent decades, antimicrobial resistance – the ability of a microorganism to resist the effects of a drug – has emerged as a serious public health concern. Multidrug-resistant Acinetobacter baumannii is a rapidly emerging pathogen in the health care setting, where it causes infections that include sepsis, pneumonia, meningitis, urinary tract infection, and others. A recent study analyzed the genomes of multidrug-resistant Acinetobacter baumannii and the bacteriophages used against it.

    Bacteriophages (often referred to simply as “phages”) are viruses that infect bacteria. They are abundant in the human gut and exert disparate effects on human health, as seen in their potential roles in resolving bacterial infections and in the pathogenesis of Parkinson’s disease. Bacteriophages are species-specific and typically only infect a single bacterial species or even specific strains within a species. In 2016, physicians in the United States used bacteriophage therapy to successfully treat a patient with multidrug-resistant Acinetobacter baumannii. During bacteriophage therapy, both the phages and their bacterial hosts replicate and evolve, which can drive resistance to the phages and impair resolution of the infection.

    The current study analyzed the genomes of the phages used in the treatment as well as their bacterial target. Their analysis revealed that not only were eight of the nine phages related (minimizing their effectiveness due to redundancy), but phage resistance emerged as early as the second day of treatment, highlighting the importance of genomic analysis of phages prior to treatment.

    These findings add to the growing body of evidence to support the use of bacteriophages against drug-resistant microbes. Learn more about bacteriophages in this interview featuring gut microbiome expert Dr. Eran Elinav.

    Read more
  • Stress accelerates immune aging. www.sciencedaily.com
    Aging Immune System Stress

    Stress ages the immune system.

    Psychosocial stress, such as that experienced with discrimination or trauma, has profound effects on the human body. For example, evidence suggests that stress alters the immune system, driving inflammatory processes and impairing antiviral responses. Findings from a recent study demonstrate that stress accelerates immune aging.

    Immune function wanes as the body ages, a phenomenon referred to as immunosenescence. This gradual deterioration of the immune system is widely considered the primary driver of the increased rate of infections and cancers in older adults. Multiple factors promote immunosenescence, including genetics, nutrition, exercise, and pathogen exposures, among others.

    The investigators analyzed blood samples taken from more than 5,700 participants over the age of 50 years who were enrolled in the Health and Retirement Study, an ongoing study of older adults living in the United States. They measured the types and characteristics of the participants' immune cells, including CD4+ naïve (immature) cells, CD4+ differentiated (mature) cells, CD8+ naïve cells, and CD8+ differentiated cells, as well as the ratio of CD4+ to CD8+. Having more immature cells is indicative of a younger immune cell profile. The participants provided information about their socioeconomic status, lifestyle practices, and lifetime exposures to various stressors, including stressful life events, chronic stress, everyday discrimination, lifetime discrimination, and life trauma.

    The investigators found that participants who had experienced more stress had fewer immature CD4+ cells and more mature CD4+ cells. Similarly, those who had experienced more stress had fewer immature CD8+ cells and more CD8+ cells. Those who had experienced high lifetime discrimination and chronic stress tended to have a lower CD4+ to CD8+ ratio, an indicator of impaired immune function. However, some of the harmful effects of stress were partly ameliorated by lifestyle factors, such as not smoking or drinking alcohol, and maintaining a healthy weight.

    These findings suggest that psychosocial stress accelerates immune aging, potentially driving disease and premature death in vulnerable groups. However, lifestyle practices may moderate this risk. Interestingly, evidence suggests that a fasting-mimicking diet promotes the return of a more youthful immune cell profile. Learn more in this clip featuring Dr. Valter Longo.

    Read more
  • Antidepressant effects of omega-3 EPA may occur in the brain even though brain content is low (it is present in microglia and involved in signaling) www.sciencedirect.com
    Brain Omega-3 Inflammation Depression Immune System Behavior

    From the article:

    It was previously assumed that because EPA is extremely low in the brain it did not cross the blood-brain barrier and any therapeutic effects it exerted would be via the periphery. However, more recent studies have established that EPA does enter the brain, but is rapidly metabolised following entry. While EPA does not accumulate within the brain, it is present in microglia and homeostatic mechanisms may regulate its esterification to phospholipids that serve important roles in cell signaling. Furthermore, a variety of signaling molecules from EPA have been described in the periphery and they have the potential to exert effects within the brain. If EPA is confirmed to be therapeutic in major depression as a result of adequately powered randomized clinical trials, future research on brain EPA metabolism could lead to the discovery of novel targets for treating or preventing major depression.

    Read more
  • Obese when compared to those with normal body fat had much higher inflammation: 53% higher CRP, 30% higher TNF-a, 17% higher WBC count, 42% higher IL6 linkinghub.elsevier.com
    Obesity Aging Metabolism Inflammation Immune System Metabolic Syndrome IL-6

    Strong link between accumulated visceral fat and chronic inflammation.

    A person’s waist-to-hip ratio compares their waist measurement to that of their hips. A high ratio can be an indicator of excess fat accumulation around the waist, often referred to as visceral fat. Findings from a 2005 study suggest that visceral fat is associated with markers of inflammation.

    Visceral fat is stored in the abdominal cavity near the liver, pancreas, and intestines. The accumulation of visceral fat is linked to increased risk of cardiovascular disease and other chronic diseases. Many factors drive visceral fat accumulation, including poor sleep, an obesogenic diet, and sugar-sweetened beverage intake, among others.

    The study involved more than 3,000 healthy males and females (18 to 89 years old) living in Greece. The investigators calculated the participants' body mass index (BMI) and measured their waist and hip circumferences. Participants provided blood samples for the assessment of inflammatory biomarkers, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), amyloid A (an apolipoprotein secreted in the acute stage of inflammation), white blood cells, and interleukin-6 (IL-6).

    The investigators found that approximately 36 percent of the males and 43 percent of the females had excess visceral fat. Approximately 20 percent of the males and 15 percent of the females had obesity. Participants with greater visceral fat had 53 percent higher CRP, 30 percent higher TNF-alpha), 26 percent amyloid A, 17 percent higher white blood cell counts, and 42 percent higher IL-6, compared to participants with normal fat distribution. The relationship between visceral fat and inflammatory markers was stronger than that between obesity and inflammation, even when considering the participants' age, income, education, and other potential confounding factors.

    These findings suggest that visceral fat and inflammatory processes are linked. The investigators posited that excess accumulation of visceral fat may increase the risk for cardiovascular disease by driving inflammation.

    Read more
  • Curcumin may act as an intervention in chronic urinary tract infection through dampening of toll-like receptors and reducing bacterial colony count pubmed.ncbi.nlm.nih.gov
    Microbiome Immune System Curcumin Microbes Toll-Like Receptors

    Curcumin reduces urinary tract infection symptoms via interaction with toll-like receptors.

    Urinary tract infections are common outpatient infections. They occur more frequently among women, and 50 to 60 percent of all women report having had at least one UTI in their lifetime. Findings from a 2017 study suggest that curcumin reduces the symptoms associated with urinary tract infections via interaction with toll-like receptors.

    Toll-like receptors comprise a family of pattern recognition receptors expressed on the surfaces of immune and other cells. They are the principal inducers of innate immunity and are responsible for the activation of transcription factors that increase the expression of proinflammatory cytokines. Chronic infections of the urinary tract, which either don’t respond to treatment or keep recurring, can occur in some people.

    Curcumin is a bioactive compound found in the roots of Curcuma longa, a type of tropical plant. It is responsible for the vibrant yellow color of the spice turmeric. Evidence suggests that curcumin exerts robust antioxidant, anti-inflammatory, and anticancer effects. Curcumin also exhibits antibacterial activity, but the compound is strain-specific.

    The study involved rats that had chronic urinary tract infections. Half of the rats received a curcumin injection, while the other half did not. The investigators measured the animals' white blood cell counts, bacterial counts (in the bladder and urine), markers of inflammation, and expression of toll-like receptor (TLR)2 and TLR4.

    They found that white blood cell counts, bacterial counts, markers of inflammation, and expression of TLR2 and TLR4 of the rats that received the curcumin injection were considerably lower than those of the rats that didn’t receive curcumin. These findings suggest that curcumin improves the symptoms of chronic urinary tract infections and reduces inflammatory responses via dampening the expression of TLR2 and TLR4.

    Read more
  • Cold treatment and sympathetic nervous stimulation increases T Regulatory cells (Tregs) in fat tissue: brown fat most of all, visceral least www.sciencedaily.com
    Immune System Cold Stress Norepinephrine Brown Fat Visceral Fat

    From the article:

    The number of obese people as well as those suffering from type 2 diabetes is increasing worldwide. Both disorders are associated with metabolic changes including amplified inflammatory responses in adipose tissue. “Previous studies have indicated that immunosuppressive regulatory T-cells – or Tregs for short – play an important role in these processes,”[…]

    [They] determined that the number of Tregs in adipose tissue increases in response to different environmental stimuli. These stimuli included a short-term cold treatment, stimulation of the sympathetic nervous system (beta-3-adrenoreceptors) or short-term high-caloric exposure. “All these stimuli supported those immunosuppressive cells directly in the adipose tissue,”

    T regulatory cell response to cold and adrenaline reduced in visceral fat:

    The magnitude of the increase in Tregs differed depending on the type of adipose tissue: it was particularly pronounced in brown fat, somewhat weaker in subcutaneous fat and weakest in visceral fat.

    Read more
  • Plasmacytoid dendritic cells (pDCs) are a special immune cell that accumulate in visceral fat, producing lymphoid structures driving secondary disease www.sciencedaily.com
    Obesity Inflammation Immune System Metabolic Syndrome Visceral Fat

    An obesogenic diet drives immune cell activation.

    Although the role of dietary fat intake in obesity is a matter of considerable controversy, research has identified complex interrelationships between dietary components, inflammation, and immune function. For example, some evidence suggests that consumption of a diet high in fat drives inflammatory processes in the central nervous system and peripheral tissues, including the liver, adipose tissue, skeletal muscle, and gut, promoting metabolic dysfunction and weight gain. Findings from a recent study suggest that a high-fat diet promotes the activity of plasmacytoid dendritic cells, a type of immune cell.

    Plasmacytoid dendritic cells, also known as natural interferon-producing cells, are critical components of both the innate and adaptive immune response. These specialized cells secrete copious amounts of type 1 interferons in response to a viral infection and then differentiate into professional antigen-presenting cells, which can stimulate T cell activity. Chronic stimulation of the plasmacytoid dendritic cells is linked with the development of autoimmune disorders and certain types of cancer. Although plasmacytoid dendritic cells are somewhat rare, they have been identified in visceral adipose tissue.

    The investigators fed multiple groups of mice either a high-fat diet or standard chow for three weeks. They gave one group of mice on the high-fat diet a drug that blocks the migration of plasmacytoid dendritic cells into the visceral adipose tissue. Then they analyzed the animals’ blood, peripheral tissue, lymphatic organs, and visceral adipose tissue for the presence of plasmacytoid dendritic cells.

    They found that after three weeks of a high-fat diet, plasmacytoid dendritic cells increased in the blood, liver, spleen, and visceral adipose tissue. The cells were especially abundant in fat-associated lymphoid clusters within the visceral adipose tissue. The animals on the high-fat diet gained weight and exhibited poor glucose tolerance, indicating metabolic dysfunction. Their visceral adipose tissue weight doubled during the three-week diet. Animals that received the drug that blocked plasmacytoid dendritic cell migration did not gain weight and demonstrated better glucose tolerance.

    These findings suggest that an obesogenic diet drives visceral and peripheral weight gain, promotes glucose intolerance, and increases immune cell activation in the visceral adipose tissue of mice.

    Read more
  • Broccoli sprout extract may promote tumor-infiltration of immune cells and drive cell death in breast cancer. onlinelibrary.wiley.com
    Breast Cancer Immune System Apoptosis Sulforaphane

    Nearly four million women living in the United States have a history of breast cancer. Evidence suggests that dietary interventions improve breast cancer outcomes and enhance survival. Findings from a recent study indicate that consumption of an isothiocyanate-rich broccoli sprout extract may improve outcomes in women with breast cancer.

    Isothiocyanates are byproducts of a reaction between compounds present in cruciferous vegetables. Isothiocyanates inhibit the activity of enzymes that transform procarcinogens into carcinogens. One of the most studied isothiocyanates is sulforaphane, which is derived from broccoli and is particularly abundant in broccoli sprouts.

    The study involved 30 women (average age, 61 years) who were about to undergo surgery to remove breast cancer tumors. The investigators randomly assigned half of the women to receive 200 micromoles of isothiocyanates from a broccoli sprout extract every day for two weeks prior to their surgery. (This daily dose of broccoli sprout extract is roughly equivalent to that provided in 500 grams – a little more than one pound – of fresh broccoli.) The remaining half of the women received a placebo. The investigators measured isothiocyanate metabolites and cytoprotective proteins in the women’s urine and biomarkers of anticancer activity in the excised tumor tissue.

    They identified multiple proteins in the participants' urine that indicated increased activity of cytoprotective pathways, including the Nrf2-mediated oxidative response pathway. They also observed changes in biomarkers of anticancer activity, including a trend toward increased levels of proteins that regulate programmed cell death and immune cells that recognize and kill cancer cells, as well as a trend toward decreased levels of proteins involved in proliferation. These changes were not statistically significant, however.

    These findings indicate that consumption of an isothiocyanate-rich broccoli sprout extract may improve outcomes in women with breast cancer. The authors posited that the absence of statistically significant findings was likely due to their small sample size and suggested further study with a larger sample.

    Read more
  • Inherited Parkinson's LRRK2 mutations promote excessive inflammatory cytokines that cross blood-brain barrier, trigger neuron damage via microglia www.sciencedaily.com
    Brain Parkinson's Aging Inflammation Immune System Blood-Brain Barrier Lipopolysaccharide

    From the article:

    Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent – the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.

    When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a “cytokine storm,” with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.

    Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.

    Read more
  • Chronic systemic inflammation induced by lipopolysaccharide can cause microglia to attack the blood-brain barrier www.sciencedaily.com
    Obesity Inflammation Immune System Toll-Like Receptors Blood-Brain Barrier Lipopolysaccharide

    Obesity promotes circulation of lipopolysaccharide. In animals, chronic systemic inflammation, experimentally induced by injection with LPS, also known as “LPS challenge,” can cause microglia into the brain to switch from protecting the blood-brain barrier to damaging it.

    From the article:

    Nearly 50 percent of all dementias, including Alzheimer’s, begins with the breakdown of the smallest blood vessels in the brain and their protective “gatekeeper cells,” according to a Keck School of Medicine of USC study.

    […]

    A key point of interest was the systemic inflammation induced by injecting the mice with an inflammation-inducing substance. Such injections resulted in the movement of microglia to the blood vessels and increased the permeability of the blood-brain barrier within a few days. Then, the microglia initially acted to protect the blood-brain barrier and limit increases in permeability, but as inflammation progressed, the microglia reversed their behavior by attacking the components of the blood-brain barrier, thus increasing the barrier’s permeability. The subsequent leakage of molecules into the brain had the potential to cause widespread inflammation in the brain and consequent damage to neurons (cells of the nerves).

    Read more
  • Spike proteins that extrude from SARS-CoV-2 promote inflammatory responses on the endothelial cells that form the blood-brain barrier. www.sciencedaily.com
    Brain Inflammation Immune System COVID-19 Blood-Brain Barrier

    SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    COVID-19 is widely regarded as a respiratory illness, but evidence suggests it affects multiple organ systems, including the central nervous system. For example, some people with COVID-19 experience headaches, nausea, vomiting, or “brain fog” – indicators of neurological involvement. Evidence from a 2020 study suggests that SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 (ACE2), a protein that is widespread among the body’s tissues and plays important roles in blood pressure control. Once inside the cell, SARS-CoV-2 replicates, triggering a robust immune response and eliciting widespread inflammation.

    The blood-brain barrier, a semi-permeable barrier that separates the blood from the brain’s extracellular fluid, prevents the entry of neurotoxic substances into the brain. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators first examined postmortem brain tissue from healthy people as well as people who had been diagnosed with hypertension (high blood pressure) or dementia to identify the presence of ACE2 in the brain blood vessels. They found that not only was ACE2 present in the blood vessels, but it was particularly abundant in people with hypertension or dementia. Then, using an in vitro model of the blood-brain barrier, they assessed the effects of exposure to the SARS-CoV-2 spike protein, the primary infectious particle on the virus. They found that exposure to the spike protein impaired blood-brain barrier function and integrity. Finally, using a tissue model that mimics the movement of fluid in the barrier, they found that the spike protein increased barrier permeability.

    These findings suggest that SARS-CoV-2 binds to ACE2 receptors in the brain and impairs blood-brain barrier function and integrity. These effects may be exacerbated in people with co-existing illnesses such as hypertension or dementia.

    Read more
  • Omega-3 pro-resolving mediators resolvins and maresins reduced production of "pathogenic" white blood cels, increased beneficial T regulatory cells www.sciencedaily.com
    Omega-3 Inflammation Immune System

    From the article:

    In the newly published work, the team examined the roles of two resolvins and one maresin in human blood lymphocytes, finding that they reduced the activation and prevented the differentiation of two types of pathogenic white blood cells, Th1 and Th17 cells. The team also found that these molecules could regulate Treg cells, a separate subset of cells that can tamp down the immune response. The team further verified these results in a mouse model deficient in these molecules. Together, these discoveries suggest that pro-resolving lipid mediators influence the balance between pathogenic Th1/Th17 and tolerogenic Treg cells, a balance that is typically altered during chronic inflammatory and autoimmune diseases.

    Read more
  • Suppression of TLR4 gene shown in animals to protect against retinal cell death associated with acute glaucoma www.sciencedaily.com
    Inflammation Immune System Eyes Toll-Like Receptors

    From the article:

    In the study, researchers showed that a rapid, sustained large increase in eye pressure in mice turns on a gene (TLR4) that activates a protein known as caspase-8. This signaling protein in turn triggers the production of inflammatory proteins that normally help mammals fight microbial infections.

    “This immune response is a double-edge sword because, while these proteins protect us from infection in a normal situation, they stimulate apoptosis (programmed cell death) in retinal cells in cases of acute glaucoma,” said Zhang, who is also a staff physician at the Veterans Affairs San Diego Healthcare System.

    To further confirm the mechanism linking high eye pressure to retinal damage, researchers showed that they could slow retinal cell death in mice with acute glaucoma by suppressing either the TLR4 gene or caspace-8 protein.

    Read more
  • Animal research suggests fragmented sleep promotes cancer through increases in TLR4 which polarize macrophages towards immune suppressive M2 type www.sciencedaily.com
    Cancer Sleep Immune System Toll-Like Receptors

    Poor sleep drives cancer growth by decreasing a type of immune cell that eliminates tumors.

    Scientists have long known that people who don’t get enough sleep are at greater risk of developing cancer. Once a person develops cancer, how long and how well they sleep can influence their disease outcome. A 2014 study implicated tumor-associated macrophages and toll-like receptor (TLR)- 4 as the primary drivers of unfavorable cancer outcomes in the setting of poor sleep.

    Tumor-associated macrophages are white blood cells that play important roles in cancer progression. M1 macrophages, which have a proinflammatory phenotype, can eliminate cancer cells. M2 macrophages, which have an anti-inflammatory phenotype, suppress immune activity and promote blood vessel growth – a critical aspect of tumor survival.

    TLR-4 is a receptor protein found on the surface of immune and other cells. TLR-4 activates transcription factors that promote the expression of pro-inflammatory cytokines. While this inflammatory response is necessary for immunity against bacterial infection, chronic activation of the TLR-4 pathway can accelerate aging and increase the risk for many diseases, including cancer.

    The investigators interrupted the sleep of normal mice and mice that lacked TLR-4, mimicking the effects of several sleep disorders. After the mice developed cancer, the investigators noted characteristics of the animals' tumors, including size, invasiveness, and the type and number of tumor-associated macrophages.

    They found that the mice that experience interrupted sleep had larger, more invasive tumors and larger numbers of tumor-associated macrophages than the mice that had uninterrupted sleep. However, these effects were not observed in the mice that lacked TLR4.

    These findings suggest that poor, fragmented sleep promotes tumor growth and invasiveness via activation of TLR4 pathways and subsequent recruitment of tumor-associated macrophages. Learn more about the varied roles TLR4 plays in human health in our overview article.

    Read more
  • TLR4 exacerbates necrotizing enterocolitis, a leading cause of death in premature newborns, by stopping enterocytes from closing wounds in intestines www.sciencedaily.com
    Inflammation Immune System Intestinal Permeability Toll-Like Receptors

    View full publication:

    Blocking signals from a key molecular receptor that normally switches on the intestine’s immune response but instead becomes too intense in the presence of stress and toxins may help reverse necrotizing enterocolitis (NEC), a leading cause of death in premature newborns.

    […]

    But Hackam’s group found that the stresses of oxygen deprivation and bombardment by bacterial toxins, conditions that can occur in premature infants with underdeveloped lungs, stimulate too much production of TLR4. Like an unstoppable alarm, the increased numbers of TLR4 blare out signals that eventually tip the cells into cellular suicide. They also stop enterocytes from migrating to close wounds in the intestines.

    Read more
  • Silencing TLR4 gene can stop process leading to cardiovascular disease in diabetics (animal study) www.sciencedaily.com
    Diabetes Immune System Blood Sugar Toll-Like Receptors Cardiovascular

    TLR4 plays a role in death of heart cells from high blood sugar.

    From the article:

    Researchers writing in BioMed Central’s open access Journal of Translational Medicine carried out a series of in vitro tests which demonstrated that TLR4 plays a critical role in hyperglycaemic cardiac apoptosis, and that silencing the gene using specific small interfering RNA (siRNA) can prevent it.

    […]

    They found that after 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated, and signs of apoptosis were evident. Silencing TLR4 resulted in suppression of apoptotic cascades. According to Min, “This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.”

    Read more
  • Butyrate may protect against graft-versus-host disease after bone marrow transplants, suggests animal research www.sciencedaily.com
    Gut Diet Microbiome Immune System Butyrate

    From the article:

    In a new study, published in Nature Immunology, researchers searched for alterations in the gut microbiome to see whether their metabolites could impact outcomes after BMT.

    They found that a metabolite called butyrate was significantly reduced in the intestinal tract of experimental mice that received bone marrow transplant. When the researchers increased butyrate in these mouse models, they saw a decrease in the incidence and severity of graft vs. host disease.

    “Our findings suggest we can prevent graft vs. host disease by bolstering the amount of the microbiome-derived metabolite butyrate,” says study lead author Pavan Reddy, M.D., the Moshe Talpaz Professor of Translational Pathology and interim division chief of hematology/oncology at the University of Michigan.

    Read more
  • TLR4 receptor involved in recognizing and triggering the innate immune system in response to bacteria may be involved in reinforcing binge drinking www.sciencedaily.com
    Brain Gut Alcohol Immune System Behavior Intestinal Permeability

    Genetic activation of TLR4 in the brain reduced binge drinking. What makes this so interesting is that alcohol consumption itself promotes intestinal permeability, which increases systemic activation of TLR4, potentially resulting in negative cardiovascular outcomes, among other things.

    From the article:

    One of the study’s most novel findings concerns TLR4’s important role in binge drinking. Science has traditionally considered TLR4 to be an innate immunity receptor involved with neuroinflammation in the brain. Scientists associated TLR4 with microglia, cells that support inflammatory responses in the brain. “What makes this finding particularly important for the field of neuroscience is that we’re showing that TLR4 plays a significant role in neurons, specifically, the neurons that are connected to the GABA receptor,” says Dr. June.

    To establish the connection between the GABA receptors, TLR4 and alcohol, the scientists manipulated this pathway in the binge drinking rodents. Dr. Aurelian was a pioneer in developing a method to inhibit gene expression, helping scientists to pinpoint the role of individual genes in the body. […] The scientists found that when they artificially stimulated the GABA receptors and TLR4 in order to simulate the good feelings binge drinkers feel when drinking alcohol, the rats lost interest in alcohol for two weeks after the procedure.

    Read more
  • New research identifies critical differences between the two types of vitamin D, with vitamin D2 having a questionable impact on human health. www.sciencedaily.com
    Vitamin D Immune System Autoimmunity

    Vitamins D2 and D3 exert differing effects on the human immune system.

    Scientists have identified five forms of vitamin D, but the two primary forms relevant to human health are ergocalciferol, commonly referred to as vitamin D2 (produced by invertebrates), and cholecalciferol (produced by mammals), commonly referred to as vitamin D3. Prescription vitamin D supplements in the United States typically provide D2, but over-the-counter dietary supplements and fortified foods typically provide D3. Considerable controversy exists regarding the bioequivalence of D2 and D3. Findings from a recent study suggest that D2 and D3 exert differing effects on the human immune system.

    Vitamin D modulates both innate and adaptive immune responses via its interactions with immune cells, including antigen presenting cells, B cells, and T cells. Evidence suggests that people with vitamin D deficiency are at greater risk of viral infection and autoimmune disorders. This is in keeping with the widely held belief that a principal role of vitamin D is to restrain, or balance, immune system activity.

    The study was part of a previous randomized placebo-controlled trial involving healthy white European and South Asian females who received 15 micrograms (600 IU) of vitamin D2 or D3 every day for 12 weeks during the winter months, when sun exposure was limited. Participants also consumed vitamin D-fortified foods (orange juice and tea biscuits) daily. The investigators used microarray analysis to measure changes in 97 of the participants' blood transcriptome (the full range of RNA molecules an organism produces) and weighed the changes against any influence of ethnic background.

    They found that while the effects of both D2 and D3 showed some overlap, the two forms of the vitamin showed distinct differences in terms of changes to gene expression. In particular, D3 switched off the activity of genes involved in the regulation of the innate and adaptive immune systems. The investigators posited that these changes could make the immune system more tolerant and therefore less likely to promote autoimmunity. They also noted that vitamin D3 (and not D2) had a dramatic effect on genes involved in activation of interferon, which plays important roles in providing protection against pathogens and cancer. The investigators' analysis revealed that some of the variation in overall gene expression was likely due to ethnic differences among the participants.

    These findings suggest that vitamins D2 and D3 exert differing effects on the human immune system, with D3s effects modulating tolerance and immunoreactivity. They also may have relevant implications for supplementation with vitamin D.

    Read more
  • Aerobic exercise (wheel running) prevents cancer tumor formation, growth, and cachexia (cancer weight loss) in mice www.sciencedaily.com
    Exercise Cancer Immune System Aerobic IL-6

    Effect of aerobic exercise on cancer in mice:

    Training mice regularly on a wheel (the mouse version of a treadmill) decreased the growth of multiple types of tumors, including skin, liver, and lung cancers. Furthermore, mice that exercised regularly had a smaller chance of developing cancer in the first place. The beneficial effects of running went beyond tumor formation and growth, extending to cancer-associated weight loss, a process termed cachexia that is seen in cancer patients. Mice that exercised regularly showed no signs of cancer-associated weight loss in the researchers' lung cancer mouse model.

    Myokine signaling from the muscles:

    The researchers say that, the production of adrenaline results in a mobilization of immune cells, specifically one type of immune cell called a Natural Killer (NK) cell, to patrol the body. These NK cells are recruited to the site of the tumor by the protein IL-6, secreted by active muscles. The NK cells can then infiltrate the tumor, slowing or completely preventing its growth. Importantly, the researchers note that injecting the mice with either adrenaline or IL-6 without the exercise proved insufficient to inhibit cancer development, underlining the importance of the effects derived only from regular exercise in the mice.

    Read more
  • Mechanical forces of pressure and movement from exercise increases the formation of bone and lymphocytes, enhancing the ability to clear infection www.sciencedaily.com
    Exercise Aging Immune System Bone

    From the article:

    Researchers from the Morrison laboratory discovered that forces created from walking or running are transmitted from bone surfaces along arteriolar blood vessels into the marrow inside bones. Bone-forming cells that line the outside of the arterioles sense these forces and are induced to proliferate. This not only allows the formation of new bone cells, which helps to thicken bones, but the bone-forming cells also secrete a growth factor that increases the frequency of cells that form lymphocytes around the arterioles. Lymphocytes are the B and T cells that allow the immune system to fight infections.

    When the ability of the bone-forming cells to sense pressure caused by movement, also known as mechanical forces, was inactivated, it reduced the formation of new bone cells and lymphocytes, causing bones to become thinner and reducing the ability of mice to clear a bacterial infection.

    Read more
  • Having "mono" increases risk for multiple sclerosis later in life. apple.news
    Immune System Virus Multiple Sclerosis Autoimmunity

    Epstein-Barr virus is one of the most common human viruses in the world. It is the primary cause of mononucleosis (often called “mono”) – a highly infectious disease that affects mostly teenagers and young adults. Findings from a recent study suggest that Epstein-Barr infection increases a person’s risk for developing multiple sclerosis.

    Multiple sclerosis is an autoimmune disorder characterized by the progressive destruction of myelin – the insulating sheath that surrounds nerves and facilitates neural transmission. The disease affects approximately 3 million people worldwide and is twice as likely to manifest in women than men. Symptoms of multiple sclerosis typically appear between the ages of 20 and 50 years.

    The study investigators analyzed blood samples from more than 10 million active duty military personnel, collected during routine health exams over a period of 20 years. From this group, they identified 801 personnel who had been tested for Epstein-Barr virus and later developed multiple sclerosis while on active duty. The investigators looked for the presence of antibodies in the blood samples that signaled past Epstein-Barr infection, as well as a protein called neurofilament light chain, a marker of myelin degeneration.

    They found that the average age at which personnel were diagnosed with Epstein-Barr infection was 20 years; multiple sclerosis onset typically occurred approximately ten years later. The risk of developing multiple sclerosis later in life was 32 times higher after having experienced Epstein-Barr infection during young adulthood. Levels of neurofilament light chain were higher among the military personnel who had experienced Epstein-Barr infection.

    These findings suggest that Epstein-Barr virus is the causal factor in the development of multiple sclerosis and underscore the need for developing vaccines against the virus. Although there is no cure for multiple sclerosis, evidence suggests that the fasting-mimicking diet may be beneficial in treating the condition. Learn about the fasting-mimicking diet in this episode featuring Dr. Valter Longo.

    Read more
  • Zinc deficiency promotes inflammation and weakens immunity, especially in older adults. pubmed.ncbi.nlm.nih.gov
    Aging Inflammation DNA Damage Immune System Zinc

    Vitamins and minerals are utilized by a wide array of enzymes that protect cells and DNA from damage. Zinc, in particular, is essential for maintaining DNA integrity and adequate antioxidant defenses. A new paper reviewing the work of Dr. Bruce Ames and others highlights the importance of zinc in promoting longevity and preventing chronic diseases.

    Zinc is a metallic mineral that is consumed in the diet from foods such as meat, shellfish, legumes, and fortified foods. Severe zinc deficiency results in growth retardation, hair loss, skin sores, and depressed immunity and is uncommon in developed nations. However, marginal deficiency, which is asymptomatic and dangerous over long periods of time, is likely very common. Children, older adults, and people with altered gastrointestinal function are particularly susceptible to zinc deficiency.

    Zinc is concentrated in the nuclei of cells where it functions to stabilize chromatin (large structures of spooled DNA) and catalyze chemical reactions for DNA repair, replication, and transcription. Along with other metals such as copper, iron, and magnesium, zinc is essential for balancing oxidative and reductive reactions in the cellular environment. One enzyme, copper-zinc superoxide dismutase, neutralizes hydrogen peroxide radicals by accepting an electron at its copper site. By absorbing reactive oxygen species, antioxidant compounds prevent damage to structures such as lipid membranes, enzymes, and DNA.

    The immune system is a major producer of hydrogen peroxide and other oxygen radicals, which attack pathogens and recycle damaged host cells. Adequate zinc intake is essential for moderating the inflammatory response. In particular, zinc inhibits activation of the NF-kappaB pathway, driving the production of inflammatory cytokines such as tumor necrosis factor-alpha. Zinc deficiency increases the risk of developing neurodegenerative and autoimmune diseases through mechanisms that involve over-activation of inflammatory pathways.

    Zinc deficiency further increases one’s risk of disease by reducing the number of pathogen-fighting cells such as antibody-producing B cells, natural killer cells, and monocytes. Reduced pathogenic immunity and increased chronic inflammation are common in old age, but they begin in middle-adulthood and progress over time in parallel, with decreasing zinc absorption and retention. Zinc supplementation in older adults reduces inflammation while increasing production of new immune cells and strengthening the body’s response to vaccines.

    Overall, zinc deficiency accelerates the aging process by impairing antioxidant production and cellular repair mechanisms, over-activating inflammatory pathways, and reducing pathogen defenses. The authors conclude there is good evidence to suggest that supplementing with at least 20 milligrams of zinc per day may be an effective strategy for reducing the adverse effects of aging on the immune system.

    Read more
  • Low levels of zinc increase risk and severity of pneumonia and antibiotic use in older adults. academic.oup.com
    Immune System Zinc

    Immune function declines with age, putting older adults at increased risk of infections such as pneumonia. Zinc is an essential nutrient that has been shown to regulate the function of white blood cells and increase immunity. Findings of a study in older adults demonstrate a link between low serum zinc and an increased incidence of pneumonia and antibiotic use.

    T cells are white blood cells that mature in the thymus, a gland located in the chest that decreases in size and function after adolescence. Zinc deficiency has been shown to accelerate thymic shrinking, reduce T cell proliferation, and suppress antibody production. Low serum zinc levels are associated with poor immune function in older adults; however, the association between zinc levels and pneumonia incidence and severity is unknown.

    The authors collected data from a trial in which 600 participants who were residents of a long-term care facility were randomly assigned to receive a vitamin E supplement (200 international units per day) for one year or a placebo. All participants were given a supplement containing 50 percent of the recommended dietary allowance of essential nutrients, including zinc, in an effort to make individuals easier to compare as a group. The authors measured the incidence and duration of pneumonia, number of antibiotic prescriptions, days of antibiotic use, death due to pneumonia, and death due to any cause.

    At baseline, risk of death due to any cause was 39 percent lower in participants with normal serum zinc levels (greater than or equal to 70 micrograms per deciliter) compared to low serum zinc levels (less than 70 micrograms per deciliter); however, zinc levels were not significantly associated with any of the pneumonia-related variables. After one year of supplementation, the incidence of pneumonia and number of new antibiotic prescriptions were about 50 percent lower in participants with normal zinc levels. These participants also experienced about four fewer days of pneumonia illness and three fewer days of antibiotic use.

    Among older adults living in residential care facilities, normal serum zinc levels reduced pneumonia incidence and severity and antibiotic use. Learn more about the role of zinc in health and longevity and which foods contain zinc in our overview article.

    Read more
  • Brain’s own immune cells "infect" healthy neurons with Alzheimer-linked beta-amyloid protein. www.nature.com
    Alzheimer's Immune System

    Alzheimer’s disease is a common neurodegenerative disorder affecting an estimated 24 million older adults worldwide. Researchers believe the disease is caused by toxic levels of beta-amyloid protein aggregates in the brain that impair neuronal function and trigger cognitive decline. While this process is partly under the influence of genes, studies also indicate links between Alzheimer’s and external factors such as head injury. Findings from a new study shed new light on this link, suggesting that events such as head trauma and stroke accelerate Alzheimer’s disease by activating one of the brain’s major immune cells and triggering an infection-like spread of amyloid-beta tangles to previously unaffected tissues.

    The researchers conducted their experiments in mice genetically engineered to carry five mutations associated with Alzheimer’s disease. While these mutations lead to brain beta-amyloid aggregations and cognitive impairments at an early age, the team uncovered that even genetically healthy brain tissue could accumulate these aggregations if implanted into the brains of these mutant mice.

    To better understand this infection-like phenomenon, the researchers examined whether the mutant brain cells of the host might import beta-amyloid particles by migrating into the transplanted tissue or making connections with its neurons. Tracking them under a microscope offered no support for this hypothesis. Instead, the team uncovered a mass migration into the implanted tissue of microglia, the main immune cells of the nervous system, specialized for scouting brain tissue for signs of injury or pathogen invasion and clearing out cellular debris.

    One possible reason for this migration is that microglia are drawn to wounds. Indeed, the microglia were particularly concentrated around the edges of the transplant and exhibited similar migrations to tiny brain lesions that the researchers generated using lasers. However, in moving from the genetically diseased to healthy tissue, the microglia dumped large numbers of beta-amyloid particles previously picked up from the degenerating host brain tissue.

    The results offer an updated picture of Alzheimer’s disease progression where the brain’s own immune cells inadvertently drive the spread of pathogenic beta-amyloid aggregations – an effect that might be aggravated by brain injury events and inflammation. While scientists are uncertain why contaminated microglia engage in this “dumping” practice, targeting the cells' activity as a way of interfering with the neurodegenerative process provides promising research opportunities.

    Read more
  • The brain can remember and resurrect immune responses to previous infections. www.scientificamerican.com
    Brain Immune System

    The brain’s inner workings have traditionally been viewed as separate from “unconscious” physiological functions like immunity. Yet, recent research has uncovered a surprising degree of reciprocal brain-immune system interaction. For example, biomarkers of peripheral immunity influence brain aging and cognition, and dopamine-rich reward circuits in the brain influence systemic antibacterial activity in immune cells. A recent study now reveals that specific brain cells store memories of the body’s past experiences with infections, potentially reawakening previous immune responses.

    The researchers first measured brain activity in a group of mice that had inflammatory bowel disease. Their measurements revealed that the bowel inflammation and its associated immune response generated a broad pattern of activity across several regions of the brain, especially the insular cortex, a region considered crucial for receiving and processing information about internal bodily states and immune system activities.

    Then, to test whether the pattern of neuronal activity in the insular cortex represented a true memory of bowel inflammation, they examined how the mice reacted when the insular neurons were reactivated four weeks after the animals' recovery from illness. The result was a near-perfect revival of the original immune response to bowel inflammation, including a surge of white blood cells to the colon, heightened activation of a range of T-cells specialized for sensing and attacking pathogens, and a spike in pro-inflammatory molecules such as interleukins and tumor necrosis factor-alpha.

    The brain-induced immune event exhibited two features that indicated it was a form of recollection. First, it was exclusively located in the colon, suggesting a relatively precise “memory” of bowel inflammation rather than a generic signal for immune defense. Second, a repeated experience with simulated bowel disease caused the insular cortex to generate a new and largely non-overlapping pattern of immune-triggering activity. This indicates that the insular cortex is capable of “remembering” distinct episodes of the body’s encounters with disease.

    This study provides some of the first causal evidence that brain cells can form memories of past immune reactions – a property that may have evolved to help bodily tissues become faster and more precise in how they tackle future infections. While the mechanisms of these neuro-immune interactions are not fully understood, the interactions offer the potential for targeted insular brain stimulation to treat severe autoimmune and inflammatory health conditions.

    Link to full publication.

    Read more
  • Patients with obesity and COVID-19 produce mostly autoimmune SARS-CoV-2 antibodies, not neutralizing. pubmed.ncbi.nlm.nih.gov
    Obesity Immune System COVID-19 Autoimmunity

    Obesity is a strong independent risk factor for COVID-19, the disease caused by the SARS-CoV-2 virus. Previous research has shown that people with obesity generate fewer antibodies in response to viral infection or vaccination; however, whether antibody quality is also affected by obesity is unknown. Findings published in a new report show that the majority of the antibodies found in people with obesity are autoimmune and not able to neutralize the SAR-CoV-2 virus, putting individuals with obesity at greater risk of severe COVID-19.

    Obesity increases the rate of inflammaging, the process of chronic low-grade inflammation that wears down the body’s tissues over time, putting people with obesity at greater risk of many diseases. Inflammaging increases the risk of autoimmunity by increasing the concentration of damaged cellular components in the blood, potentially triggering the immune system to generate antibodies against its own cells. Previous research has shown that many patients with severe COVID-19 generate autoimmune antibodies that increase the risk of long-term complications. Because people with obesity experience increased baseline inflammaging, they may be at greater risk of developing long-term autoimmune complications for COVID-19; however, no published studies have yet addressed this concern.

    The investigators collected blood from 15 participants with a lean BMI (less than 25) and 15 participants with an obese BMI (greater than 30) who tested positive for SARS-CoV-2. The investigators also collected blood from 30 participants who had not had a SARS-CoV-2 infection and were matched for age, sex, and BMI. The researchers measured the concentration of neutralizing antibodies (meaning antibodies that bind to the SARS-CoV-2 spike protein and prevent viral entry into cells), non-neutralizing antibodies, and autoimmune antibodies.

    Participants with obesity had fewer SARS-CoV-2 antibodies than participants with a lean BMI, confirming previous reports. While all 15 SARS-CoV-2-positive participants with a lean BMI had circulating neutralizing antibodies, only a few participants with obesity did. The researchers found that SARS-CoV-2 infection increased the concentration of autoimmune antibodies in all patients, but the concentration of autoimmune antibodies was always higher in participants with obesity. Finally, they found that participants with the highest concentration of autoimmune antibodies also had the highest levels of serum C-reactive protein, a marker of chronic inflammation, suggesting that inflammation is integral to developing autoimmunity.

    These data confirm previous reports that obesity reduces the effectiveness of the immune response in COVID-19 patients and increases the risk of autoimmunity.

    Read more
  • Immune cell function fluctuates throughout the day. apple.news
    Immune System Circadian Rhythm

    Dendritic cells are white blood cells that play critical roles in launching the body’s immune response. Typically found in peripheral tissues such as the skin, dendritic cells migrate to the lymph nodes, where they interact with T cells to induce immune responses against pathogens, vaccines, and cancer cells. Findings from a new study suggest that dendritic cell migration is subject to circadian rhythm.

    Circadian rhythms are the body’s 24-hour cycles of biological, hormonal, and behavioral patterns. They modulate a wide array of physiological processes, including the body’s production of hormones that regulate sleep, hunger, metabolism, and others. Ultimately, circadian rhythms influence body weight, performance, and disease susceptibility.

    The authors of the study collected skin samples from normal (wild type) mice, mice that lack circadian rhythm, and humans at four distinct times during the day and night, corresponding to morning, day, evening, and night. Mice circadian rhythms are similar to humans', but since mice are nocturnal, the rhythms are “flipped.” The authors quantified the number of dendritic cells in the skin samples using immunofluorescence imaging.

    They found that the migration patterns of dendritic cells followed a circadian pattern, peaking during the rest phase, which occurred early afternoon for mice and early morning for humans. The drivers of this migration were CCL21 (an antimicrobial cell signaling protein) and adhesion molecules (components of an active T-cell mediated immune response), both of which vary in expression along a gradient throughout the day.

    These findings suggest that dendritic cell migration into lymph vessels is subject to circadian rhythm. They also underscore the importance of considering the time of day at which vaccines or immunotherapy treatments are administered.

    Read more
  • Macrophages may need lactate and pyruvate for effective nerve regeneration. apple.news
    Immune System Lactate

    Peripheral nerves have the ability to regenerate following trauma, surgery, and exposure to medications and toxins; however, the rate of regeneration is often very slow. The molecular signals that encourage regeneration dissipate over time so that regeneration ends too soon to effectively heal long nerves. Authors of a new report elucidate the role of monocarboxylate transporters and macrophage metabolism is promoting nerve regeneration.

    Macrophages (Greek for “large eaters”) are white blood cells that remove pathogens and cellular debris by engulfing and digesting them, making macrophages essential for cellular repair and immunity. Macrophages coordinate tissue regeneration efforts among multiple cell types by secreting a variety of cytokines to recruit additional support cells. In the case of nerve regeneration, macrophages promote the migration of Schwann cells, which produce myelin, to the site of damaged axons.

    Monocarboxylate transporters (MCTs) facilitate the movement of small energy molecules such as lactate and pyruvate into cells. When oxygen levels are low or metabolic demand is high, monocarboxylate compounds can be used instead of glucose for cellular energy. Emerging research demonstrates the role of MCTs in the progression of central nervous system disorders and neurodegenerative diseases; however, the role of MCTs on peripheral nerve injury is unknown.

    The authors utilized multiple mouse models for their study. First, they compared sciatic nerve regeneration following injury among mice that did not express the MCT-1 protein in one of four cell types: macrophages, perineurial cells, Schwann cells, or dorsal root ganglia neurons. Second, they observed sciatic nerve regeneration in mice that over-expressed the MCT-1 protein in macrophages. Finally, they tested the ability of macrophage adoptive cell transfer, in which macrophages that are isolated from bone marrow, cultured in vitro, and reinfused, to improve nerve regeneration in mice lacking the MCT-1 protein.

    Removal of the MCT-1 protein from macrophages significantly reduced nerve regeneration as demonstrated by poor recovery of electrical activity over six weeks following nerve injury; however, removal of MCT-1 from perineurial cells, Schwann cells, or dorsal root ganglia neurons did not impair nerve regeneration. Removal of MCT-1 from macrophages also increased pro-inflammatory cytokines and decreased pro-regenerative cytokine concentrations in the damaged tissue. Not all of these altered cytokines are produced by macrophages, indicating that MCT-1 removal in macrophages modulates the activity of the broader immune system. MCT-1 removal from macrophages impaired mitochondrial function and reduced ATP production, worsening the ability of macrophages to adapt to stressful stimuli and/or high metabolic demands. These macrophages were also less able to clear cellular debris.

    Mice that over-expressed the MCT-1 protein in macrophages had significantly faster never regeneration compared to normal mice. MCT-1 expression did not affect motor, sensory, or behavioral recovery following nerve injury. Finally, in mice that did not express MCT-1 protein in macrophages, adoptive transfer of cells led to a complete recovery from nerve injury.

    The authors concluded that the MCT-1 protein in macrophages is essential for coordinating nerve regeneration and that adoptive macrophage transfer may be an important therapy in treating nerve injury. It is important to note that the MCT-1 protein transports ketones in addition to lactate and pyruvate. This invites speculation that certain forms of intense exercise, which promotes lactate uptake and utilization throughout the body, or nutritional ketosis may improve nerve regeneration; however, this theory has yet to be tested experimentally.

    Read more
  • Eating spices reduces chronic inflammation. academic.oup.com
    Inflammation Immune System Polyphenol Lipopolysaccharide

    Obesity causes chronic inflammation, which promotes atherosclerosis and cardiovascular disease. Previous research suggests that spices such as cinnamon, cumin, and ginger exert short-term anti-inflammatory effects; however, studies with longer durations are needed to confirm these findings. Authors of a recent study found that four weeks of spice consumption reduced inflammation and altered monocyte function in adults at risk of cardiometabolic disease.

    Monocytes are white blood cells that respond to infection by promoting inflammation. Obesity and dyslipidemia cause inappropriate activation of monocytes, promoting chronic inflammation in the arteries. Pro-inflammatory monocytes carrying excess lipids, called foam cells, accumulate in arterial walls, narrowing the arteries and restricting blood flow. Consuming spices that contain anti-inflammatory bioactive compounds may help reduce cardiovascular disease risk.

    The authors recruited 71 participants and assigned them to consume a standard American diet with added spices in three doses: low (a dash), medium (a quarter teaspoon), or high (a half teaspoon). Participants consumed each dose of spices for four weeks and completed the doses in random order. The spice mixture contained the most common spices used in the United States, the most abundant of which were cinnamon, coriander, ginger, cumin, and parsley. Participants provided blood samples at multiple points throughout the study. Finally, the investigators isolated monocytes from the participants’ blood and exposed the cells to bacterial endotoxin in order to promote inflammation.

    Compared to baseline, participants had lower fasting serum levels of the pro-inflammatory cytokine interleukin-6 following four weeks of the medium dose spice blend. The monocytes from these participants also secreted less interleukin-6 when challenged with bacterial endotoxin. Participants consuming the medium and high spice blends had fewer foam cells and more conventional monocytes than participants consuming the low spice blend.

    The authors concluded that spices reduced fasting inflammation and altered monocyte behavior. They did not know why the medium dose was more effective in reducing inflammation than the high dose, but they hypothesized that the high dose of spices may have contained such a high level of polyphenols that it promoted oxidative stress. More research is needed to test this hypothesis. This study was funded by the McCormick Science Institute.

    Read more
  • mRNA vaccines provide long-lasting immunity and protection from SARS-CoV-2 variants. www.bloomberg.com
    Immune System Vaccine COVID-19

    SARS-CoV-2 mRNA vaccines (e.g., Moderna and Pfizer-N-BioTech) are effective in preventing infection and have even greater efficacy in preventing severe COVID-19 illness and hospitalization. However, many people in the United States received their vaccine early in 2021, more than six months before the time of this writing. Whether the protection afforded by vaccination lasts as time passes and more SARS-CoV-2 variants emerge is unclear. Findings of a report published in August provide insights into long-term immunity following vaccination or SARS-CoV-2 infection, concerns about emerging variants, and implications for vaccination boosters.

    During infection with a virus, the innate immune system immediately produces inflammation to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. White blood cells such as macrophages and neutrophils participate in the innate response, while B and T cells facilitate the adaptive response. Plasma B cells are responsible for producing antibodies; however, these cells steadily decrease in number over time. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection. Memory T cells are also responsible for “remembering” viruses in this way. Memory CD4+ T cells rapidly respond to reinfection to support inflammation and antibody production. Memory CD8+ T cells, also called cytotoxic T cells, bind to virus-infected host cells and order them to undergo apoptosis (i.e., programmed cell death).

    The authors of the report analyzed a set of 342 blood samples collected from 61 participants at one, three, and six months following vaccination. This group of participants included SARS-CoV-2 naive individuals (i.e., those who were never infected with the virus) and SARS-CoV-2 recovered individuals. The investigators measured the concentration of circulating antibodies that bind to the SARS-CoV-2 receptor binding domain protein and spike protein. They also measured the concentration of memory B cells and T cells and characterized these cells’ response when challenged with SARS-CoV-2 antigens.

    The concentration of serum antibodies declined over time, but was still detectable at six months post-vaccination. mRNA vaccination produced memory B cells that respond to the receptor binding domain protein of the Alpha, Beta, and Delta variants, called cross-binding memory. These memory B cells had significantly more hypermutation, the process by which B cells rearrange their DNA in order to produce antibodies to new antigens, and increased in concentration between three and six months post-vaccination. Cross-binding B cells were more common in SARS-CoV-2 recovered patients than naive patients. mRNA vaccination also increased memory CD4+ and CD8+ T cells.

    The immune response to mRNA vaccination and infection with the SARS-CoV-2 virus evolves over time, which may have implications for the future use of booster vaccines. These results should be considered with caution as this research has yet to be peer-reviewed.

    Read more
  • Fecal microbiota transplantation from young mice reverses aging effects. www.sciencedaily.com
    Brain Aging Microbiome Immune System Microbes

    Declines in brain function are common with age owing to metabolic and immune alterations that include changes to the gut microbiota, the community of microorganisms that inhabit the intestines. While a diverse microbial community with many species of beneficial bacteria is associated with improved nutrition and reduced inflammation, older adults (especially residents of long-term care facilities) have perturbations in microbiota composition that increase the risk for cognitive decline and frailty. Findings of a report released this month show that fecal microbiota transplantation from young to aged mice reverses age-associated cognitive impairment.

    Fecal microbiota transplantation is a therapy in which microbes are isolated from the stool of a donor, processed, filtered, and administered to a recipient by nasogastric tube or enema. Previous research demonstrates the efficacy of fecal microbiota transplantation in treating infection with Clostridium difficile, a hospital-acquired infection that is difficult to treat with antibiotics, and a growing list of other diseases such as inflammatory bowel disease, metabolic syndrome, neurodevelopmental disorders (e.g., autism), and autoimmune diseases. Fecal microbiota transplantation improves health partially by increasing microbiota alpha diversity, meaning the number of species in an individual’s microbiota, also called “richess.” A microbiota with high richness is more likely to contain key beneficial species, such as those that produce neuroprotective short chain fatty acids.

    Given the wide range of diseases associated with gastrointestinal microbiota composition, its effects on aging are an area of intense interest. Prior investigations have demonstrated that transfer of the fecal microbiota from aged mice to young mice alters immunity, neurogenesis, and cognition; however, the consequence of fecal transplantation from young mice to aged mice is unknown.

    The investigators performed their experiment using young and aged male mice. They assigned aged mice to receive a fecal microbiota transplant from either a young mouse (the experimental group) or aged mouse (the control group). For further comparison, the researchers also assigned a group of young mice to receive a fecal microbiota transplant from another young mouse. Mice received the fecal microbiota transplant treatments once per day for three days, then twice weekly for four weeks. The mice completed a battery of tests to assess cognitive function. The researchers collected fecal samples in order to sequence the DNA of the microbiota and blood samples in order to measure hormones, cytokines, and other immune markers before and after the four weeks of treatment. Finally, they analyzed changes to gene expression and metabolism in the hippocampus, the brain region most-associated with age-related cognitive decline.

    At baseline, young and aged mice had distinctly different microbiota composition. Following four weeks of microbiota transplantation, young mice, aged mice receiving a young transplant, and aged mice receiving an aged transplant all had similar microbiota composition. Aged mice tended to have more over-reactive T cells, dendritic cells, and macrophages, especially in the lymph nodes that line the intestines. Aged mice also showed enlargement of microglia (the predominant immune cells in the brain), a common feature of neurodegenerative diseases. Microbiota transplantation from young mice reversed these age-related effects on brain and peripheral immunity. Amino acid metabolism in the hippocampus, which is necessary for neurotransmission and cognition, was impaired in aged mice, but restored following microbiota transplantation from young mice. Finally, the improved hippocampal metabolism in aged mice that received a young microbiota transplant translated to increased learning and long-term memory and reduced anxiety-related behaviors compared to aged mice receiving an aged microbiota transplant.

    These results reveal the potential benefits of fecal microbiota transplantation from young donors as a therapy to promote healthy aging.

    Read more
  • A ketogenic diet may reduce COVID-19 severity. www.embopress.org
    Diet Immune System Ketogenic Diet

    Aging impairs the body’s ability to fight infection due to chronic low-grade inflammation and a decrease in antibody-producing T cells. Consequently, 80 percent of deaths due to COVID-19 in the United States have been among adults 65 years of age and older. Researchers investigated the use of a ketogenic diet in mice as a strategy for treating COVID-19.

    A ketogenic diet is a high fat, low carbohydrate diet. Adherence to a ketogenic diet reduces blood glucose levels, which are associated with increased inflammation. Adopting a ketogenic diet may be an effective strategy for limiting excessive inflammation, especially in older adults, who are more likely to have poor blood glucose control.

    The SARS-CoV-2 virus, the cause of COVID-19 illness, induces lung inflammation. In severe cases, patients may need mechanical ventilation to breathe and may have long-lasting respiratory problems after recovery. Previous COVID-19 research has shown that white blood cells such as neutrophils and monocytes accumulate in the lungs. There they become more reliant on glucose, accelerate their mitochondrial metabolism, and produce more damaging oxidative compounds, contributing to unchecked inflammation and disease severity.

    The researchers used mice that express the human angiotensin-converting enzyme (ACE) 2 receptor, which is the point of entry for the SARS-CoV-2 virus in the lungs and other organs. They fed young adult mice and older adult mice either a standard diet or a ketogenic diet for five days before exposing them to a hepatitis virus that closely mimics the SARS-CoV-2 infection in humans. The mice continued their assigned diet for an additional seven days following infection. The investigators measured markers of inflammation and metabolic function.

    Older mice had significantly higher levels of inflammation and metabolic dysfunction at the beginning of the study. Upon infection, they had greater inflammation in the heart, adipose tissue, and hypothalamus; worse pneumonia symptoms and increased blood clot formation; and were more likely to die due to infection, compared to younger mice. The increased inflammation was due to an increase in neutrophil accumulation and a decrease in tissue-protective T cells in the lungs. A ketogenic diet reprogrammed metabolism and the immune system to a greater extent in older mice by increasing the number of beneficial T cells and reducing the number of harmful monocytes in the lungs, leading to less inflammation overall and reduced disease severity.

    Although this study was conducted in mice, the authors concluded that a ketogenic diet may be a potential treatment for SARS-CoV-2 infection in older adults due to its ability to modulate immune function and dampen excessive inflammation.

    Read more
  • A compound in blueberries dampens the body's immune response and reduces inflammation. www.eurekalert.org
    Inflammation Immune System Polyphenol

    A critical component of the body’s immune response to pathogens, damaged cells, or irritants is inflammation. Chronic inflammation, however, can promote the development of chronic inflammatory disorders. Findings from a new study suggest that pterostilbene, a polyphenolic compound present in blueberries, can reduce the risk of developing chronic inflammatory disorders by altering the activity of dendritic cells and T cells.

    Pterostilbene is a polyphenolic compound that demonstrates antioxidant, anti-inflammatory, and anti-cancer properties, as well as many other beneficial effects. Closely related to resveratrol, pterostilbene is found in blueberries and a tropical tree commonly known as heartwood.

    Dendritic cells and T cells are key elements of the body’s immune responses. Dendritic cells initiate the adaptive immune response, which in turn activates T cells. Activated T cells produce interleukin (IL)‐2 to facilitate their proliferation and subsequent differentiation into various helper T cells, including Th1, Th2, Th17, or regulatory T cells (Tregs). Over-activation of Th1, Th2, and Th17 cells can lead to immune disorders, such as inflammatory bowel diseases, atopic dermatitis, and psoriasis. Conversely, Treg cells produce IL‐10, an anti-inflammatory protein, to reduce inflammation and impair disease progression.

    The authors of the study used an in vitro cell culture system to assess the effects of pterostilbene and related compounds on immune cell response. They looked at the activity of dendritic cells and T cells in the presence or absence of the compounds to evaluate their immunosuppressive activity.

    They found that pterostilbene suppressed T cell‐proliferation and decreased the Th1 and Th17 population in a dose‐dependent manner but did not affect the population of Th2 cells. The presence of pterostilbene markedly increased Treg differentiation was markedly increased.

    Then the authors of the study assessed the effects of pterostilbene on mice that had ulcerative colitis, a type of inflammatory bowel disease. They gave the mice pterostilbene in their drinking water for a week. They found that the mice that consumed the pterostilbene had fewer symptoms associated with their disease and lower levels of tumor necrosis factor-alpha, a type of pro-inflammatory protein.

    Taken together, these findings indicate that pterostilbene exhibits immunosuppressive activity by directing T cell differentiation toward Treg cells rather than Th1 and Th17 cells. Furthermore, oral consumption of pterostilbene may reduce colonic inflammation associated with an inflammatory bowel disease.

    Read more
  • Vitamin and mineral supplementation in older adults improves self-reported health status. www.sciencedaily.com
    Immune System Micronutrients

    Vitamins and minerals are essential micronutrients that play critical roles in immune function, especially vitamins C and D and zinc, a mineral. Many older adults living in developed countries are at risk for micronutrient deficiency. Findings from a new study indicate that micronutrient supplementation may improve immune function in people over the age of 55 years.

    The randomized controlled trial involved 42 healthy older adults (55 to 75 years old). Half of the participants took a commercial multivitamin supplement that was formulated to support immune function, and the other half took a placebo. The multivitamin provided 1 gram of vitamin C and 10 milligrams of zinc per day, and the intervention lasted 12 weeks. Before and after the intervention, the authors of the study took blood samples from the participants to assess their micronutrient status, immune function, and immune status. The participants provided self-reported assessments of their overall health.

    At the end of the study, the authors found that multivitamin supplementation improved the participants' vitamin C and zinc status as well as their self-reported health status, but it didn’t change vitamin D status or measures of immune function or status. These findings demonstrate that healthy older adults may benefit from multivitamin supplementation, but larger studies are needed to confirm.

    Read more
  • T lymphocytes may bridge the gap in COVID-19 immunity. www.sciencedaily.com
    Immune System COVID-19

    Immunity and susceptibility to COVID-19 is an area of ongoing research. Findings from a recent study indicate that T cells that react to the SARS-CoV-2 spike protein are present in both COVID-19 patients and healthy people unexposed to the virus.

    T lymphocytes, also known as T cells, are part of the body’s adaptive immune response. T cells are produced when the body encounters a viral, bacterial, or fungal pathogen. T cells come in a variety of forms, including helper T cells, cytotoxic T cells and memory T cells.

    Previous research has demonstrated the presence of SARS-CoV-2-reactive T cells circulating in the blood of unexposed people. The current study characterized T cell reactivity against the SARS-CoV-2 spike protein in COVID-19 patients and unexposed people.

    The authors of the study combined isolated immune cells from both COVID-19 patients and unexposed people to synthetic segments of the SARS-CoV-2 spike protein. They found reactive memory T-helper cells in 83 percent of people with COVID-19 and 35 percent of people who had not been exposed to the virus. The T cells of COVID-19 patients reacted to both the N- and the C-terminal ends of the SARS-CoV-2 spike protein. However, the T cells of unexposed individuals reacted primarily to the C-terminal end of the spike protein — a region that shares similarity with “common cold” coronaviruses.

    These findings suggest that there is some pre-existing immunity in the general population against SARS-CoV-2, possibly due to exposure to the common cold coronaviruses. Larger studies are needed to determine if cross-immunity will affect the clinical outcomes of COVID-19 patients.

    Learn more about COVID-19 in these Q&As featuring Dr. Rhonda Patrick, posted April 14 and June 10.

    Read more
  • Evidence mounts that exposure to "common cold" coronaviruses may yield some protection against SARS-CoV-2. www.sciencedaily.com
    Immune System COVID-19

    Scientists are learning more about how people respond to SARS-CoV-2, the new coronavirus responsible for the ongoing COVID-19 pandemic. Findings from a recent study suggest that prior exposure to “common cold” coronaviruses may generate the production of SARS-CoV-2 specific T cells.

    SARS-CoV-2 belongs to the Coronaviridae family of RNA viruses. There are four coronaviruses known to circulate among the world’s population and transmit the “common cold.”

    A healthy person’s response to a viral infection involves a coordinated effort between the innate and adaptive immune systems. Whereas the innate immune system — the first line of defense — involves barrier functions, such as those provided by the skin, the adaptive immune system includes distinct cell types that work together to neutralize the virus. T cells kill virus-infected cells and present viral fragments to B cells, which in turn produce antibodies against the virus. Some T cells, known as memory T cells, are long-lived and persist in the body to defend against future attacks by the same virus or related viruses.

    Previous research on other viral infections has demonstrated that cross-reactive T cells circulating in a person’s blood may protect them from developing severe disease. The current study investigated the T cell response to the SARS-CoV-2 virus and explored the features of cross-reactive immunity.

    The authors of the study examined blood collected from healthy people prior to the emergence of the SARS-CoV-2 virus. They detected CD4+ T cells in the blood of approximately half of the people unexposed to the SARS-CoV-2 virus. The authors speculate that these observations indicate the existence of cross-reactive immunity between SARS-CoV-2 and the coronaviruses that cause the “common cold.” They submit that this cross-reactivity may be a hopeful sign. However, it may also complicate COVID-19 vaccine trials if some subjects have pre-existing immunity.

    These findings suggest that prior exposure to a related coronavirus stimulates the production of SARS-CoV-2 reactive T cells that persist in the body. Whether these T cells help an individual clear COVID-19 remains to be seen.

    Learn more about COVID-19 in these Q&As featuring Dr. Rhonda Patrick, posted April 14 and June 10.

    Read more
  • T cells may be key to providing long-lasting immunity to SARS-CoV-2. www.sciencedaily.com
    Immune System Virus COVID-19

    Much remains unknown about SARS-CoV-2, the new coronavirus responsible for the on-going COVID-19 pandemic. Two important questions revolve around why some people become severely ill while others experience no symptoms, and the associated implications for long-term immunity. Findings from a recent study suggest that prior exposure to related coronaviruses may affect the production of T cells that affect disease severity and immunity.

    SARS-CoV-2 belongs to the Coronaviridae family of RNA viruses. There are six coronaviruses known to infect humans, having effects that range from severe pneumonia (SARS-CoV-1 and MERS-CoV) to the “common cold”.

    A healthy person infected with a virus mounts a coordinated immune response involving distinct cell types that work together to neutralize the invading pathogen. The adaptive immune system includes T cells that kill virus-infected cells and display antigens (viral fragments) to B cells, which in turn produce antibodies against the virus. Research demonstrates that T cells persist in the body longer than antibodies. For example, 11 years after recovering from SARS-CoV-1 infection, memory T cells were still present, while antibodies were undetectable two to three years after the disease resolved.

    Proteins are highly conserved among related coronaviruses. The current study investigated whether the blood of people who had recovered from SARS-CoV-1 or SARS-CoV-2 contained immune factors that would react to isolated SARS-CoV-2 viral proteins.

    The authors of the study identified SARS-CoV-2 virus-specific memory T cells in the blood of people who had recovered from COVID-19. The authors then analyzed the blood of 15 SARS-CoV-1 resolvers, 17 years after infection. They observed that all individuals possessed viral-specific T cells that responded not only to SARS-CoV-1 viral proteins but also to SARS-CoV-2 proteins. These results suggest that T cells provide long-lasting protection and offer some cross-protection between SARS-CoV-1 and SARS-CoV-2. The researchers even detected SARS-CoV-2 specific T cells in 19 out of 37 people unexposed to either SARS-CoV-1 or SARS-CoV-2, suggesting they had encountered a related coronavirus, possibly one responsible for the “common cold”.

    These findings suggest that T cells produced against SARS-CoV-2 will provide long-term immunity. This research also supports the idea that prior infection with a related coronavirus affords some immunity against SARS-CoV-2 infection, and might explain the variations observed in infection rates and disease severity.

    Read more
  • Recovered COVID-19 patients carry T-cells that might promote long-term immunity. www.sciencemag.org
    Immune System Virus COVID-19

    Critical elements of the body’s immune system are T-cells, a class of lymphocytes that promote an appropriate immune response and actively engage in the destruction of pathogens. Findings from two new studies suggest that people who are infected with SARS-CoV-2, the virus that causes COVID-19, have T-cells that target the virus.

    The first of the two studies analyzed blood samples collected 20 to 35 days after the onset of symptoms in 20 non-hospitalized COVID-19 patients who were no longer symptomatic. All of the COVID-19 patients that were tested carried SARS-CoV-2 specific helper T-cells and nearly three-quarters carried natural killer T-cells.

    The authors of the study also investigated whether people who haven’t been infected with SARS-CoV-2 might have immunity to the virus by analyzing blood samples from 2015 to 2018, well before the pandemic began. They found that roughly half of the samples had helper T-cells that recognized SARS-CoV-2.

    Similar results were found in the second study, which analyzed blood samples from 18 people with COVID-19. Their findings demonstrated that 83 percent of COVID-19 patients carried helper T-cells and 35 percent of uninfected people carried helper T-cells. The authors of both studies suggested that this cross-reactivity likely stems from a previous infection with coronaviruses that cause colds.

    These findings suggest that a subset of the population might be better equipped to fight of infection from SARS-CoV-2 due to previous exposure to other coronaviruses.

    Read more
  • The betacoronaviruses can induce immune responses against one another, generating neutralizing antibodies and/or cross-reactive antibodies. www.ncbi.nlm.nih.gov
    Immune System COVID-19

    Betacoronaviruses are a subfamily of the coronaviruses – a group of related viruses that cause illness in birds and mammals, including humans. Members of this subfamily include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS), MERS-CoV (which causes Middle East respiratory syndrome, or MERS), SARS-CoV-2 (which causes COVID-19), and HCoV-OC43 (which causes the common cold). A 2013 study found that betacoronaviruses generate cross-reactive antibodies against SARS-CoV in serological testing.

    Serological tests detect antibodies present in the blood following a response to a specific infection, such as SARS or COVID-19. Previous studies have found that SARS-CoV-1 can generate antibodies against HCoV-OC43 (which could offer cross-immunity). Similarly, HCoV-OC43 can generate cross-reactive antibodies against SARS-CoV-1 (which could generate false positives on serological antibody tests).

    The seroprevalence study involved 94 game-food animal handlers, 28 SARS patients, and 152 healthy blood donors in Southern China. The authors of the study used indirect immunofluorescence and neutralizing antibody tests to screen for antibodies.

    They found that two of the animal handlers had antibodies against HCoV-EMC and SARS-CoV-1, with low levels of neutralizing antibodies. However, 17 of the SARS patients had neutralizing antibodies against HCoV-OC43. None of the healthy blood donors had any antibodies against either virus.

    These findings suggest that betacoronaviruses can induce immune responses against one another, generating neutralizing antibodies and/or cross-reactive antibodies against each other. This could confound serological surveillance studies investigating the prevalence of SARS-CoV-2 infection, while also raising the possibility for cross-immunity. No data currently exist demonstrating that betacoronaviruses generate cross-reactive and/or neutralizing antibodies against SARS-CoV-2. Both scenarios are probable.

    Read more
  • Pneumonia-causing bacteria release large amounts of hydrogen peroxide to inactivate the inflammasome and evade the immune response www.sciencedaily.com
    Vitamin C Inflammation Immune System

    From the article:

    The researchers found that bacteria such as pneumococci release large quantities of hydrogen peroxide, and that this causes inactivation of inflammasomes thereby weakening the immune system […] Our studies demonstrate that hydrogen peroxide is an inhibitor of an important component of the inflammatory machinery suggesting that the mechanism we have uncovered is a common strategy employed by many microbes to thrive within us,“ says Saskia Erttmann, first author in the study and former member of Nelson Gekara’s research group.

    Role for vitamin C:

    “One of the best known substances with the ability to neutralize hydrogen peroxide and that could hence boost anti-bacterial immunity are vitamins such as Vitamin C found in fruits. Perhaps the old adage ‘an apple a day keeps the doctor away’ is not off the mark,” adds Nelson Gekara.

    Read more
  • Orally administered vitamin C with an average dose of 2 grams per day reduced the length of ICU stay on average by 8.6% www.sciencedaily.com
    Vitamin C Immune System

    From the article:

    Vitamin C metabolism is changed in many conditions that involve physiological stress, such as infections, surgery, traumas, and burns, in which case vitamin C levels can decline dramatically. Although 0.1 grams per day of vitamin C can maintain a normal plasma level in healthy persons, much higher doses, up to 4 grams per day, are needed for critically ill patients to increase their plasma vitamin C levels to the range of normal healthy people. Therefore, high vitamin C doses may be needed to compensate for the increased metabolism in critically ill patients.

    […]

    Dr. Harri Hemilä from the University of Helsinki, Finland, and Dr. Elizabeth Chalker from the University of Sydney, Australia, carried out a systematic review of vitamin C for ICU patients. They identified 18 relevant controlled trials, and 12 of them were included in the meta-analysis on the length of stay. On average, vitamin C administration shortened ICU stay by 7.8%. In six trials, orally administered vitamin C with an average dose of 2 grams per day reduced the length of ICU stay on average by 8.6%.

    Read more
  • Vitamin C rapidly improves emotional state of acutely hospitalized patients [1 in 5 in acute-care have scurvy levels of vitamin C] www.sciencedaily.com
    Vitamin C Inflammation Depression Immune System

    Vitamin C, which has previously been shown in some studies to reduce inflammatory markers in conditions like rheumatoid arthritis, may improve emotional state of acutely hospitalized patients.

    From the article:

    Patients administered vitamin C had a rapid and statistically and clinically significant improvement in mood state, but no significant change in mood occurred with vitamin D, the researchers discovered. […] About one in five acute-care patients in our hospital have vitamin C levels so low as to be compatible with scurvy,“ added Hoffer.

    Vitamin C, which concentrates in immune cells called neutrophils and lymphocytes at concentrations 50 to 100-times greater than plasma, play an important role in generating the so-called oxidative burst used by these cells to attack invading bacteria.

    Read more
  • Large doses of vitamin C up to 8 grams per day might reduce duration of common cold. www.sciencedaily.com
    Vitamin C Immune System

    The bulk of scientific research on the effectiveness of vitamin C in fighting infection has centered on reducing the symptoms and duration of the common cold. Much of the studies have used doses of approximately 1 gram per day. Findings from a 2017 study suggest that larger doses might reduce a cold’s duration.

    Although most adults typically have only one or two colds per year, cold symptoms are the reason for many lost days of work or school. Some evidence suggests that the financial costs associated with having a cold are similar to those associated with having high blood pressure or a stroke.

    The author of the study reviewed the findings of two randomized trials focused on the effectiveness of vitamin C in reducing cold symptom duration. One of the trials had four treatment groups: one group that took a placebo, two groups that took 3 grams per day, and one group that took 6 grams per day. The 6-gram dose reduced cold symptom duration by about 17 percent – roughly twice as much as that observed with only 3 grams. The placebo had no effect on symptom duration. The other trial had three treatment groups: one that took 4 grams per day, one that took 8 grams per day, and one that took a placebo. Taking 8 grams per day reduced symptom duration by 21 percent, compared to the placebo group.

    These findings suggest that large doses of oral vitamin C might reduce the duration of symptoms associated with the common cold, but self-dosing should commence as soon as cold symptoms appear for the greatest benefit.

    Read more
  • US military scientists working to develop a therapeutic strategy against SARS-CoV-2. www.defenseone.com
    Immune System Protein COVID-19

    There are currently no vaccines to prevent infection with SARS-CoV-2, the virus that causes COVID-19. Although at least one clinical trial of an investigational vaccine is currently underway, the release of such a vaccine could take months or even years. Scientists at DARPA, the Defense Advanced Research Projects Agency, are working to develop a therapeutic strategy against SARS-CoV-2 using monoclonal antibodies.

    Antibodies are proteins that identify pathogens for destruction by the immune system. They arise from different cell lineages and bind to multiple epitopes – regions on viral proteins to which immune cells bind to drive a targeted immune response. Monoclonal antibodies, on the other hand, are made by identical immune cells cloned from a single, unique parent cell. They bind to a single, specific epitope.

    DARPA’s research is part of the Pandemic Prevention Program, or P3. Their goal is to determine which monoclonal antibodies the body produces when it encounters a particular virus, such as SARS-CoV-2, and then stimulate the body’s production of those antibodies. The process involves sequencing the RNA of B-cells taken from a person who has recovered from a particular pathogen and then producing antibodies against the pathogen. The antibodies can then be injected into a healthy person to promote immunity or injected into a sick person to facilitate recovery.

    This strategy can serve as a sort of stopgap measure until a vaccine is developed. Although identifying and producing these antibodies is a lengthy process, DARPA is working to facilitate discovery and accelerate capacity to produce the antibodies at scale.

    • Read this review of COVID-19 monoclonal antibody research for more information.
    Read more
  • Potential targets for immune responses to novel coronavirus have been identified, a crucial step in vaccine development. www.eurekalert.org
    Immune System Virus Protein COVID-19

    Coronaviruses, a genus of the Coronaviridae family, are enveloped viruses with a large positive-strand RNA genome. The recently identified SARS-CoV-2, the cause of the disease known as COVID19, is one of seven coronaviruses known to infect humans. Others include SARS-CoV (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). A team of scientists recently identified several epitopes in the SARS-CoV-2 virus, a crucial step in vaccine development strategies.

    Epitopes are regions on viral proteins that immune cells bind to drive a targeted immune response. Most epitopes are approximately five or six amino acids in length. A typical full-length viral protein sequence may contain many different epitopes to which antibodies can bind.

    The authors of the study drew on data from the Immune Epitope Database as well as Virus Pathogen Resource, a compilation of information about known pathogenic viruses. The team compiled known epitopes from other coronaviruses, mapped the corresponding regions to SARS-CoV-2, and used the information to predict likely epitopes.

    They identified several specific regions in SARS-CoV-2 that have high homology to the SARS virus, indicating that SARS-CoV is the closest related virus to SARS-CoV-2. Specifically targeting these epitopes may generate immunity to related coronaviruses and promote resistance to viral evolution.

    Read more
  • Obesity promotes diversity and virulence of influenza virus. www.eurekalert.org
    Obesity Immune System Protein

    Global estimates indicate that more than half of all adults are either overweight or obese. Obesity carries many health risks because it impairs the body’s immune response and creates a pro-inflammatory environment. In particular, being obese increases the disease severity of influenza infection. A recent study suggests that the impaired immune response commonly exhibited in people who are obese promotes the emergence of more virulent influenza strains.

    Influenza is a highly contagious respiratory infection caused by the influenza virus. More than 20,000 people die every year in the United States from influenza-related complications. Many different influenza viruses exist, and they undergo constant change, necessitating regular changes to influenza vaccines. Some of the changes to the influenza virus are due to the health and nutritional status of infected hosts. For example, diet-induced oxidative stress, micronutrient status, and aging can influence influenza virus virulence.

    The authors of the study serially infected lean and obese mice with the influenza virus to replicate the spread of influenza within the real-world setting. They found that serial infection of obese mice promoted changes in the virus that produced more virulent strains of the virus. The key driver associated with these changes was an impaired interferon response. Interferons are proteins produced by the body’s cells as a defensive response to viruses. This delayed interferon response also occurred in obesity-derived human bronchial epithelial cells.

    These findings suggest that obesity promotes influenza virus diversity and virulence and underscores concerns about the growing obesity problem.

    Read more
  • Sauna use reduces pneumonia risk in healthy, middle-aged men. www.telegraph.co.uk
    Immune System Sauna Protein

    Sauna use promotes mild hyperthermia, which, in turn, induces a wide array of physiological responses. These responses reduce oxidative stress and inflammation and activate cellular defense systems that provide protection against many diseases. Data from a 2017 study suggest that sauna use reduces the risk of developing certain chronic or acute respiratory illnesses, including pneumonia.

    Pneumonia is an acute respiratory illness characterized by cough, fever, chills, and difficulty breathing. It is a common complication of influenza and other viral infections (including the newly emerging coronaviruses) as well as bacterial infections. Pneumonia affects people of all ages, but children, older adults, and people who are immunocompromised are most vulnerable.

    The study, which drew on data from a population-based prospective cohort study of more than 2,000 healthy middle-aged men (42 to 65 years old), was conducted in Finland, where most people have a home sauna. The average sauna exposure reported in the study was approximately 20 minutes per session at 79°C (174°F).

    The data were adjusted for body mass index, smoking status, education level, alcohol consumption, total energy intake, socioeconomic status, physical activity, inflammatory status (measured by C-reactive protein), and history of diabetes, heart disease, asthma, bronchitis or tuberculosis. They revealed that the frequency of sauna use was inversely associated with the incidence of respiratory illness, especially pneumonia. Men who used the sauna two to three times weekly were 27 percent less likely to develop pneumonia than those who used the sauna once weekly or not at all. Men who used the sauna four to seven times weekly were 41 percent less likely to develop pneumonia compared to infrequent or non-users.

    The authors of the study suggested that sauna’s protective effects may be due to reduced oxidative stress associated with hyperthermia or direct beneficial effects on lung tissue.

    Read more
  • Exposure to influenza viruses during childhood may provide partial lifelong protection against distantly related influenza. www.eurekalert.org
    Immune System Virus

    Early life environmental exposures play key roles in our ability to launch an effective immune response due to a phenomenon referred to as “immunological imprinting” – the process by which the immune system fights infections after previous exposure to a pathogen. A commonly held theory was that previous exposure to an influenza virus conferred no immunological protection against subsequent exposure. However, new data suggest that immunological imprinting due to exposure to subtypes of influenza viruses during childhood may provide partial lifelong protection against other subtypes.

    Influenza is a highly contagious respiratory infection caused by the influenza virus. Complications from influenza sicken or kill hundreds of thousands of people worldwide each year. Although children and elderly people are typically among the most vulnerable to influenza infection, some subtypes of influenza disproportionately affect young, healthy adults.

    The authors of the study analyzed large surveillance data sets from the Arizona Department of Health Services, spanning 22 years of influenza seasons. The Centers for Disease Prevention and Control define “influenza season” as occurring between epidemiological week 40 (usually early October) of one year and week 39 of the subsequent year.

    Their analysis revealed that immunological imprinting shapes a person’s seasonal influenza risk and emphasized that childhood exposures can imprint a lifelong immunological bias toward particular influenza subtypes. However, newer antibody responses acquired later in life did not provide the same strength of protection as responses imprinted in childhood following the first exposure. The authors of the study postulated that the low mortality rates associated with some influenza subtypes may increase as cohorts of exposed people age.

    Link to study: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008109

    Read more
  • Early life bacterial exposures influence immune health. www.the-scientist.com
    Immune System Salt

    The skin microbiota forms the body’s first line of defense against pathogens and external threats. Changes in environmental exposures can drive bacterial dysbiosis, a condition in which the overall makeup of the skin microbiota is altered. Bacterial dysbiosis is associated with allergies and sensitivities. A new study suggests that exposure to Acinetobacter bacteria early in life provides protection against inflammatory disorders and allergies. Acinetobacter bacteria are ubiquitous in the environment and are commonly found in soil.

    The study was conducted among 180 children living in Karelia, a region that straddles the geopolitical borders of Finland and Russia. Whereas the Finnish side of Karelia is modernized, the Russian side has maintained a traditional lifestyle that involves farming and animal work. The children from the two regions were examined for symptoms of allergies and sensitivities to common allergens when they were between the ages of 7 and 11 years and again when they were between the ages of 15 and 20 years. Samples of the children’s skin and nasal microbiota were collected for analysis.

    The prevalence of allergies and allergen sensitivities was 3 to 10-fold higher among Finnish children, compared to Russian children. In addition, Russian children rarely exhibited hay fever or peanut sensitivity. Generally, these findings were replicated at the 10-year follow-up examination. The children’s skin and nasal microbiota demonstrated notable differences. In particular, the Russian children’s microbiota had a diverse, abundant population of Acinetobacter bacteria. These findings suggest that early life exposures modulate the risk of developing allergies and allergen sensitivities later in life.

    Read more
  • Brake dust air pollution may have the same harmful effects on immune cells as diesel exhaust. www.eurekalert.org
    Immune System Pollution

    Air pollution from diesel exhaust contains a mixture of both toxic chemicals and particulate matter. Many studies have found associations between exposure to diesel exhaust and subsequent poor health outcomes such as increased asthma, heart disease, and cancer. Findings from a new study suggest that brake dust air pollution may have some of the same harmful effects on health as diesel exhaust.

    Brake dust is a form of air pollution that consists of metal particles generated from mechanical abrasion from brakes. These particles are small enough to be inhaled deep into the lungs, where they drive the production of reactive oxygen species, promoting inflammation and altering the function of immune cells. Approximately 20 percent of the particulate matter in air pollution is from brake dust.

    The study was conducted in macrophages (a type of immune cell) exposed to brake dust obtained from a brake pad testing factory. Following exposure to the dust, the macrophages were challenged with a bacterial pathogen to determine the cells' ability to initiate an immune response and carry out phagocytosis, the process by which macrophages engulf and destroy pathogens.

    The cells demonstrated dose-dependent decreases in mitochondrial depolarization (a process that inhibits the production of mitochondrial reactive oxygen species), increased secretion of immune-related cytokines, and decreased phagocytosis. Following 24-hour incubation in a brake pad particle-free environment, the macrophages regained their ability to carry out an appropriate immune response.

    Although this research was performed in cells and future research will need to confirm the effects brake dust has on animals, these findings suggest that exposure to brake pad abrasion particles may be as harmful as exposure to diesel exhaust. They also highlight the importance of pollution mitigation strategies in public health interventions.

    Read more
  • Stressed mitochondria leak DNA fragments that induce inflammation. www.sciencemagazinedigital.org
    Immune System Mitochondria Protein Autoimmunity

    Oxidative stress drives many disease processes. In mitochondria, in particular, it promotes the release of mitochondrial DNA into surrounding cytosol where it can trigger cellular responses involved in autoimmunity.

    A critical aspect of mitochondrial DNA release is the formation of pores created by the oligomerization of specific proteins called voltage-dependent anion channels (VDACs), which are found in the outer mitochondrial membrane. A new study in a mouse model of lupus suggests that inhibition of VDAC oligomerization blocks mitochondrial DNA release, preventing subsequent immune responses.

    These findings suggest that inhibition of VDAC oligomerization may be an alternative therapeutic approach for a wide range of diseases likely associated with mitochondrial DNA release, such as lupus and Parkinson’s disease.

    Read more
  • Supercentenarians have high level of cytotoxic T cells, which can kill cancer cells. www.sciencedaily.com
    Cancer Aging Immune System

    Supercentenarians – people who live to be 110 years of age or older – have long healthspans, free of disease and the physical and cognitive decline that commonly accompany aging. A critical factor in their long, healthy lives is a robust immune system. Findings from a new study reveal that supercentenarians have high levels of cytotoxic CD4 T-cells, a specialized type of white blood cell.

    CD4 T-cells are key elements in the body’s antigen-specific immune response. They destroy virus-infected and malignant cells by triggering apoptosis – a type of cellular self-destruct mechanism that rids the body of damaged or aged cells. CD4 T-cells are considered “helper” cells in that they assist other cells in the immune response.

    The authors of the study collected circulating immune cells in the blood of seven supercentenarians and five controls, who were between the ages of 50 and 80 years. They found that the supercentenarians had considerably higher levels of CD4 T-cells than the controls, and these CD4 T-cells had unique cytotoxic capabilities. Furthermore, they found that the cytotoxic cells had arisen via clonal expansion, the process by which daughter cells arise from a single parent cell.

    Cytotoxic CD4 T-cells are rare, even among young people, but they play key roles in immunosurveillance and can kill cancer cells. These findings shed light on how supercentenarians maintain good health throughout their lives.

    Read more
  • Mice fed a high-fat, low-carbohydrate diet were better able to combat the flu virus and had better survival rates than mice fed a normal diet. www.sciencedaily.com
    Ketosis Immune System Protein Carbohydrates Weight Loss Ketogenic Diet

    More than 20,000 people die every year in the United States from influenza-related complications. Findings from a new study demonstrate that a ketogenic diet confers protection against the influenza virus and improves survival rates in mice.

    A ketogenic diet is a high fat, moderate protein, low carbohydrate eating pattern that causes the body to oxidize fat to produce ketones for energy. The ketogenic diet has been used in the clinical setting to reduce seizures in children and is being investigated for the treatment of traumatic brain injury, Alzheimer’s disease, weight loss, and cancer.

    The authors of the study fed a ketogenic diet or regular chow to mice for seven days and then infected them with influenza virus. The mice that ate the ketogenic diet lost less weight, maintained better blood oxygen levels, and had improved survival rates compared to the mice that ate the regular chow. In addition, the mice on the ketogenic diet had higher levels of specialized T-cells in their lungs that enhanced airway cell mucus production to improve lung barrier function.

    Interestingly, the beneficial effects of a high fat diet were only observed with the ketogenic diet. Feeding the mice a high-fat, high-carbohydrate diet or providing exogenous ketones in the diet had no beneficial effects against influenza virus.

    Read more
  • African traditional herbs hsv cure
    Immune System Dairy

    My boyfriend and I met three years ago on herpes dating site so we discovered we are +ve from the beginning of our relationship, that we both had genital herpes. My first outbreak was the ABSOLUTE worst experience, I was so sick. We suffered for one year plus, had constant outbreaks and then finally we decided to both respectively take Dr Utu African Traditional Herbs as advised by friends. His herb is Not much bitter or sour taste. Dosage two times daily every day for four weeks, and honest to goodness it was a miraculous herbs. We were on it for not more than two weeks when we noticed total change. ‘couldn’t wait for four weeks. It was third week and five days we used the herbs. Then we went for test and was already hsv2 negative, the both of us. Neither of us have had any lesion, outbreak or symptoms till date. For traditional and permanent hsv cure, Dr Utu is the key. Contact him on [email protected] or direct WhatsApp or phone +2347032718477

    Read more
  • Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection www.sciencedirect.com
    Alzheimer's Immune System Virus Protein

    Summary

    Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid are hallmarks of Alzheimer’s disease (AD) pathology. We recently reported Aβ is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate Aβ antimicrobial activities. Thus, infection can seed and dramatically accelerate β-amyloid deposition. Here, we show Aβ oligomers bind herpesvirus surface glycoproteins, accelerating β-amyloid deposition and leading to protective viral entrapment activity in 5XFAD mouse and 3D human neural cell culture infection models against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6A and B. Herpesviridae are linked to AD, but it has been unclear how viruses may induce β-amyloidosis in brain. These data support the notion that Aβ might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote Aβ amyloidosis.

    Read more
  • Role of dietary transition metals on host microbiota and risk of disease www.gutmicrobiotaforhealth.com
    Nutrition Gut Diet Microbiome Metabolism Immune System Micronutrients Iron Protein

    Transition metals are required cofactors for many proteins that are critical for life, and their concentration within cells is carefully maintained to avoid both deficiency and toxicity. To defend against bacterial pathogens, vertebrate immune proteins sequester metals, in particular zinc, iron, and manganese, as a strategy to limit bacterial acquisition of these necessary nutrients in a process termed “nutritional immunity.” In response, bacteria have evolved elegant strategies to access metals and counteract this host defense. In mammals, metal abundance can drastically shift due to changes in dietary intake or absorption from the intestinal tract, disrupting the balance between host and pathogen in the fight for metals and altering susceptibility to disease. This review describes the current understanding of how dietary metals modulate host-microbe interactions and the subsequent impact on the outcome of disease.

    https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30262-2

    Read more
  • Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity | Microbiome | Full Text microbiomejournal.biomedcentral.com
    Microbiome Immune System Pregnancy Antibiotics

    Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.

    Results - In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells.

    Conclusion - Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.

    Read more
  • Gut microbiota resilience as an emerging measure of health - Gut Microbiota for Health www.gutmicrobiotaforhealth.com
    Gut Microbiome Biomarkers Immune System

    Although gut microbiota profiles differ remarkably between healthy individuals, several features have been suggested to define a “healthy gut microbiome”. First of all, our gut microbiota can be understood, in many cases, to be redundant given that many bacterial species have similar functions. Furthermore, a healthy gut microbiome is temporally stable and resistant to perturbations and, over time, is more similar to itself than to that of another healthy person. Finally, a healthy gut microbiome is resilient, which means that it returns to a healthy state after a perturbation. For example, after antibiotic treatment, our gut microbiota usually recovers to its previous state a few weeks or months later. As such, a plausible definition of microbial health does not comprise a single static state, but rather a dynamic equilibrium. Meanwhile, when a perturbation stimulus becomes chronic and leads to an altered stable gut microbiome that causes harm to the host, this is called dysbiosis. Also see the following for detailed discussion of microbiome as emerging biomarker of health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577372/

    Read more
  • Brain inflammation found to be 30% higher in people suffering with obsessive-compulsive disorder. www.eurekalert.org
    Brain Omega-3 Inflammation Depression Immune System Anxiety Iron

    There’s very good evidence for systemic inflammation being implicated in mental disorders more generally, but also depression specifically. See the FoundMyFitness video entitled “The Underlying Mechanisms of Depression” to learn about some of the interesting experiments establishing the connection between immune dysfunction and symptoms of depression.

    This study, however, seems to suggest that people with obsessive-compulsive disorder actively have 30% higher brain-related inflammation.

    FTA:

    A chemical dye measured the activity of immune cells called microglia, which are active in inflammation, in six brain areas that play a role in OCD. In people with OCD, inflammation was 32 per cent higher on average in these regions. Inflammation was greater in some people with OCD as compared to others, which could reflect variability in the biology of the illness. […] Another notable finding from the current study - a connection between resisting compulsions and brain inflammation - provides one indicator. At least nine out of 10 people with OCD carry out compulsions, the actions or rituals that people do to try to reduce their obsessions. In the study, people who experienced the greatest stress or anxiety when they tried to avoid acting out their compulsions also had the highest levels of inflammation in one brain area. This stress response could also help pinpoint who may best benefit from this type of treatment.

    In light of the fact that we now know the body’s immune system is afforded direct access to the brain via a network of lymphatic vessels in the meninges, it puts managing systemic inflammation in a whole new light.

    While we may be a long way away from finding a “cure” for people suffering from these disorders, it does make multi-pronged inflammation reduction approaches that much more appealing.

    This could possibly include…

    … and yes, possibly targetted drugs as well. The point is, by establishing inflammation as a missing link in these disorders it opens up a lot of different possible “treatments” that might have a cumulative effect! Interesting times.

    Read more
  • Clinical trial shows whole grains modestly increase good gut bacteria, lower inflammatory gut bacteria, improve immune cells. www.sciencedaily.com
    Microbiome Inflammation Immune System Fiber Gluten

    New clinical trial shows that people that were given whole grains had a modest improvement in a good type of gut bacteria, modestly lowered inflammatory gut bacteria, and modestly increased memory T cells after 6 weeks compared to those given refined grains. Since this study compared gut bacteria, inflammatory biomarkers, and immune cells in people given whole grains versus refined grains it is difficult to draw any conclusions about whole grains compared to no grains. However, there have been other intervention trials that have shown whole grains lowered inflammatory biomarkers possibly through their effect on the microbiome. Also, this intervention trial was only 6 weeks which may also account for the modest effect on the microbiome. Things are probably much more complicated and have a lot to do with gene polymorphisms (which affect an individual’s glucose response), gut health, gluten sensitivity, and other factors. I do not think any absolute conclusions can be drawn from this study but still interesting to think about.

    Read more
  • People with the highest fiber intake had ~80% greater chance of living long & healthy life out of all other dietary factors looked at. www.sciencedaily.com
    Gut Aging Microbiome Inflammation Depression Immune System Carbohydrates

    other factors including total carbohydrate intake, glycemic index, glycemic load, and sugar intake. Successful aging was defined as including an absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases including cancer, coronary artery disease, and stroke.

    The gut is a major source of inflammation and also the major regulator of the immune system. Fermentable fiber feeds the beneficial bacteria in the gut which then prevents them from being forced to cannibalize the gut barrier (which causes inflammation) and it allows them to produce signaling molecules (short chain fatty acids) which make the immune system better. Also, many foods that contain fiber such as vegetables and fruits also have many important micronutrients and other plant compounds that play a role in successful aging. For more on the importance of fiber in successful aging watch my interview with the authors of The Good Gut, Drs. Justin and Erica Sonnenburg: https://youtu.be/gOZcbNw7sng

    Read more
  • Fasting-like diet kills autoimmune cells & replaced them with healthy cells & improved symptoms in MS patients. www.sciencedaily.com
    Brain Fasting Immune System Multiple Sclerosis Autophagy Dairy Autoimmunity Ketogenic Diet

    This fasting-like diet also promotes regeneration of the myelin in mice with multiple sclerosis. In human patients with multiple sclerosis, the fasting-like diet led to improvements in symptoms if followed by a Mediterranean diet or a ketogenic diet.

    Here is the fasting-like diet that humans were given: Day 1 – pre-fasting followed by Day 2-8 – very low calorie diet. Day 1-prefasting consists of an 800 kcal (about 40% of normal caloric intake similar to mouse Day1 FMD) monodiet (fruit, rice, or potatoes) by preference of individuals. On the following day patients were recommended to use an oral laxative, Natrium Sulfuricum (20-40 g). FMD consisted of 100 ml vegetable broth or vegetable juice with 1tablespoon of linseed oil 3 times daily, plus additional calorie-free liquids. The daily calorie intake was predefined with 200 – 350 kcal (10-18% of normal caloric intake similar to mouse Day 2-3 FMD). Patients were advised to drink 2-3 L of unsweetened fluids each day (water, and herbal teas) and to use an enema if tolerated. After the 7-day fasting period solid foods were stepwise reintroduced for three days, starting with a steamed apple at day 8. After the fasting and refeeding period a normocaloric, plant-based Mediterranean diet was maintained until study end.

    Read more
  • New 20-page report on cryotherapy just released! Cold shock boosts norepinephrine up to 5-fold & increase type of immune cell that kills tumor cells. www.foundmyfitness.com
    Exercise Brain Alzheimer's Aging Metabolism Inflammation Memory Immune System Norepinephrine Protein

    This 20-page report explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. Rhonda discusses how cold exposure increases norepinephrine up to 5-fold in the brain and what the temperature and duration needed to do this are, how norepinephrine has an effect on mood, vigilance, focus, and attention, how cold exposure increases cold shock proteins including one in the brain that repairs damaged synapses and in muscle prevents atrophy, how cold-induced norepinephrine lowers inflammation and pain by decreasing the levels of 3 inflammatory mediators, how chronic cold shock may increase immune cell numbers and particularly a type of immune cell that kills cancer cells, how cold exposure increases metabolic rate, the number of mitochondria, and the burning of fat, what the effects of different cold exposure temperatures and timing are on athletic performance, recovery time, and muscle mass, and the differences between various types of cold shock modalities, including cold water immersion and whole body cryotherapy.

    Read more
  • Beta-hydroxybutyrate produced from a ketogenic diet, fasting, or high-intensity exercise dampens inflammation via blocking of the NLRP3 inflammasome www.sciencedaily.com
    Exercise Diet Ketosis Inflammation Fasting Immune System NLRP3 Ketogenic Diet

    From the article:

    BHB is a metabolite produced by the body in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet. Dixit said it is well known that fasting and calorie restriction reduces inflammation in the body, but it was unclear how immune cells adapt to reduced availability of glucose and if they can respond to metabolites produced from fat oxidation.

    Working with mice and human immune cells, Dixit and colleagues focused on how macrophages – specialized immune cells that produce inflammation – respond when exposed to ketone bodies and whether that impacts the inflammasone complex.

    The team introduced BHB to mouse models of inflammatory diseases caused by NLP3. They found that this reduced inflammation, and that inflammation was also reduced when the mice were given a ketogenic diet, which elevates the levels of BHB in the bloodstream.

    Read more