Category: Immune System

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How Macrophages Control an Uncooperative Meal

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A macrophage digesting a yeast cell (yellow). Credit: NIH

Certain pathogens such as Salmonella have developed strategies to protect themselves from the macrophages’ digesting attempts, causing severe Typhoid infections and inflammations. Scientists report in Nature Metabolism how the inter-organellar crosstalk between phago-lysosomes and mitochondria restricts the growth of such bacteria inside macrophages.

Signals from the digestion cell organelle

As scavenger cells, macrophages have a very prominent digestion organelle, the phago-lysosome, where engulfed microorganisms are commonly degraded into pieces and become inactivated. “It has long been known that the molecule TFEB (Transcription factor EB) is important for the regulation of the phago-lysosomal system. More recent evidence also suggested that TFEB supports the defense against bacteria,” said Max Planck Institute group leader Angelika Rambold.

She and her team wanted to understand how exactly TFEB mediates its anti-bacterial role in macrophages. They confirmed earlier findings showing that a broad range of microbes, bacterial and inflammatory stimuli activate TFEB and thus the phago-lysosomal system.

“It made sense that pathogen signals trigger TFEB as macrophages need a more active digestion system quickly after they devour a meal of bacteria. But, interestingly, the experiments also revealed an additional strong effect of TFEB activation on another intracellular organelle system — mitochondria. This was completely unexpected and novel to us,” said Angelika Rambold.

Instructing mitochondria to increase anti-microbial activity

Composed of inner and outer membranes, mitochondria are the primary sites of cellular respiration and release energy from nutrients. Moreover, the mitochondria in immune cells were recently identified as sources of anti-microbial metabolites.

By using a broad experimental tool set, the investigators identified the pathway controlling an unexpected crosstalk between lysosomes and mitochondria. “Macrophages make use of extensive inter-organellar communication: the lysosome activates TFEB, which shuttles into the nucleus where it controls the transcription of a protein called IRG1. This protein is imported into mitochondria, where it acts as a major enzyme to produce the anti-microbial metabolite itaconate,” explained Angelika Rambold.

Exploiting organelle communication to control bacterial infections

The researchers investigated whether they could make use of this newly identified pathway to control bacterial growth. “We speculated that activating this pathway could be used to target certain bacterial species, such as Salmonella,” said Angelika Rambold. “Salmonella can escape the degradation by the phago-lysosomal system. They manage to grow inside macrophages, which can lead to the spreading of these bacteria to several organs in an infected body,” explained Alexander Westermann, collaborating scientist from the University of Würzburg.

When the researchers activated TFEB in infected macrophages in mice, the TFEB-Irg1-itaconate pathway inhibited the growth of Salmonella inside the cells. These data show that the lysosome-to-mitochondria interplay represents an antibacterial defense mechanism to protect the macrophage from being exploited as a bacterial growth niche.

In light of the increasing emergence of multi-drug resistant bacteria, with more than 10 million expected deaths per year by 2050 according to the various expert groups, it becomes important to identify new strategies to control bacterial infections that escape immune mechanisms. A promising path could be to use the TFEB-Irg1-itaconate pathway or itaconate itself to treat infections caused by itaconate-sensitive bacteria. According to the researchers from more work is needed to assess whether these new intervention points can be successfully applied to humans.

Source: Max Planck Institute of Immunobiology and Epigenetics

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Rare Immune Cells are Key in Mounting a Defence Against Candida

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The oral fungal pathogen Candida albicans (red) produce hyphae that allow attachment of another fungus Candida glabrata (green). Yeast cells of Candida glabrata (green) adhere to Candida albicans hyphae (red) both in static culture (left, scanning electron microscopy) and under biofilm conditions of flow (right, confocal fluorescence microscopy).
Credit: Edgerton Lab, State University of New York at Buffalo

Candida, a distant cousin of baker’s yeast is notorious for causing various types of thrush that can be a major nuisance, but it can also lead to an invasive and occasionally fatal infection. In a study in the journal Nature Immunology, a research team uncovered a previously unknown defense mechanism employed by the immune system in fighting Candida infections.

In healthy individuals, Candida is present in the microbiome in the gut and on the skin. Normally, Candida is held in check by the immune system, but it can occasionally grow excessively, invading the lining of the mouth, the vagina, the skin or other parts of the body. In severe cases, it can spread to the bloodstream and from there to the kidneys. Such life-threating infections may occur in weakened immune systems. Antibiotics can also unleash local or invasive Candida eruptions by wiping out competing, beneficial bacteria.

Until now, the immune cells that got most of the credit for defending the body against Candida were the small, round lymphocytes of the T cell type, called TH17. These cells were also the ones to take the blame when this defence failed.

In the new study, postdoctoral fellow Dr Jan Dobeš, working together with colleagues in Abramson’s lab, discovered that a powerful commando unit of TH17 cells capable of fighting Candida cannot be generated without crucial early support from an entirely different contingent: a subset of rare lymphoid cells known as type-3 innate lymphoid cells, or ILC3, that express a gene called the autoimmune regulator, or Aire

The two groups of cells belong to the two different arms of the immune system, which, like normal soldiers and specialised ‘commando’ units, join forces against a common enemy. The Aire-ILC3s – part of the more ancient, innate arm – spring into action almost immediately upon encountering a threat – in this case, a Candida infection. The TH17s belong to the immune system’s more recent, adaptive arm, which takes several days or even weeks to respond, but which launches a much more targeted and potent attack than the innate one.

The scientists found that as soon as Candida starts infecting tissues, the Aire-ILC3s engulf the yeast whole, chop them up and display some of the yeast pieces on their surfaces. In this way, the bits are presented to the TH17s, a few of which are generally on call in the lymph nodes, ready for an infection alert. This kind of presentation instructs the specialised T cells to start dividing rapidly, soaring in number from a few lone commandos to several hundred or even thousands of Candida-specific fighters, capable of destroying the yeast at the sites of infection.

“We have identified a previously unrecognised immune system weapon that is indispensable for orchestrating an effective response against the fungal infection,” Abramson said.

Abramson became intrigued by Candida because it commonly leads to severe, chronic infections in people with a rare autoimmune syndrome caused by defects in the Aire gene. Abramson’s lab had conducted extensive studies of this gene, helping to clarify its role in preventing autoimmune disorders. That research, as well as studies by other scientists, had shown that Aire-expressing cells in the thymus instruct developing T cells to refrain from attacking the body’s own tissues. When Aire is defective, T cells fail to receive proper instructions, consequently causing widespread autoimmunity that wreaks havoc in multiple body organs. But one puzzle remained: Why would Aire-deficient patients suffering from a devastating autoimmune syndrome also develop chronic Candida infections?

While trying to complete the Aire puzzle, Dobeš and colleagues found that outside the thymus, Aire is also expressed in a small subset of ILC3s in the lymph nodes. The researchers then genetically engineered two groups of mice: One lacked Aire in the thymus, and the other group lacked it in the ILC3s in the lymph nodes. The first group developed autoimmunity but was able to successfully fight off Candida. In contrast, those in the second group, the ones lacking Aire in ILC3s, were without autoimmunity, but were unable to generate numerous Candida-specific TH17s. Consequently, they failed to effectively eliminate Candida infections. In other words, without Aire-expressing ILC3s, the specialised T cells needed for fighting Candida were not produced in sufficient numbers.

“We found an entirely new role for Aire, one that it plays in the lymph nodes – turning on a mechanism that increases the numbers of Candida-fighting T cells,” Dr Dobeš explained.

An Aire-ILC3 cell (green) “kisses” a Candida-fighting TH17 cell (red), telling it to start dividing (top row), but it ignores other T cells that do not specialize in fighting Candida (bottom row)

These findings open up new directions of research that in the future may help develop new treatments for severe Candida, and possibly for other fungal infections. The newly discovered mechanism might, for example, help produce large numbers of Candida-fighting T cells to be used in cell therapy. If scientists one day decode the signals by which Aire-ILC3s boost T cell proliferation, they might serve as the basis for new therapies.

Source: Weizmann Institute of Science

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Airway Immune Risks of Fourth Generation e-Cigarettes

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Photo by Nery Zarat on Unsplash

Fourth-generation e-cigarettes, such as Juul devices, are associated with unique changes in markers of immune responses inside our airways, according to a new peer-reviewed paper in the American Journal of Respiratory and Critical Care Medicine.

Third-generation e-cigarettes include vape pens and box mods. Fourth generation include nicotine-salt-containing e-cigarettes, such as Juul products, and disposable e-cigarettes, which have become increasingly popular, especially after the recent FDA ban on the sale of Juul products.

Researchers in the lab of Professor Ilona Jaspers at the UNC School of Medicine found that users of fourth-generation nicotine-salt-containing devices display a unique mix of cellular biomarkers indicative of immune suppression.

“Our work demonstrates the importance of considering device type in future clinical, epidemiological, and mechanistic studies on the health effects of e-cigarettes,” said Prof Jasper, who led the study. “We also think this research can help regulators determine which products cause the most severe types of biological changes in airway cells important for maintaining proper health.”

E-cigarettes have become popular in the last decade. Some started used them to quit smoking, believing vaping was a safer alternative, both in the short-term and long-term. Also, because electronic cigarettes don’t contain tar, consumers assumed vaping decreased their risk of cancer down the road.

“It’s impossible to know if vaping decreases cancer risk or many other long-term conditions,” Prof Jaspers said. “It took 60 years of research to show that smoking causes cancer.” In contrast, e-cigarettes have only been around for about 15 years. “Still, the research from our lab and many others has shown many of the same acute biological effects in the airways that we have documented in smokers,” she said. “And we’ve seen some changes to cells and immune defences in people who vape that, frankly, we’ve never seen before, which is very concerning.”

A major concern for researchers, doctors, and public health officials is the fact that teenagers who would not have otherwise tried cigarettes began using e-cigarettes, which contain nicotine – with its attendant health implications – and thousands of chemicals, many of which are FDA-approved for eating but not inhaling.

Several studies have documented that inhaling chemical-laden nicotine aerosols suppresses the immune responses in the respiratory tracts of smokers and e-cigarette users. Some studies, including some at UNC, have detailed how different chemicals in various e-cigarettes, including chemicals that make up thousands of different flavours, have adverse effects on airway cells. The Jaspers lab, which has been at the forefront of such research, set out to study the effects of different varieties of e-cigarette devices. For this study, her team collected central airway (sputum) samples from non-smokers, smokers, and users of both third-generation and fourth-generation e-cigarette devices.

They found that users of fourth-generation e-cigarettes had significantly more bronchial epithelial cells in their sputum, suggestive of airway injury because normally, bronchial epithelial cells make up an intact barrier in the airways and are not found in sputum samples. Levels of two proteins, sICAM1 and sVCAM1, were significantly lower in fourth-generation e-cigarette users compared to all other groups. These proteins are important in fighting infections and other disease.

In addition, proteins are important for overall immune defence were significantly lower in fourth versus third generation e-cigarette users. Lower of these proteins – CRP, IFN-g, MCP-1, uteroglobin, MMP-2, and VEGF – indications immune system depression. “Another key finding of the study was that, when examining the mixture of immune markers overall rather than one by one, fourth generation e-cigarette users had the most distinguishable changes out of all of the groups, indicating a shift away from immune homeostasis,” said the study’s lead author, Elise Hickman, PhD.

The study did not demonstrate that e-cigarettes cause cancer, emphysema, COPD, or other long-term diseases associated with long-term cigarette smoking. But researchers think that altering immune responses in the respiratory tract over the course of many years, especially for teens, could play a major role in the development of long-term health conditions and in susceptibility to inhaled pathogens.

Source: University of North Carolina

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Regulatory T Cells Play a Surprising Role in Hair Growth

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Photo by Engin Akyurt on Unsplash

In an unexpected finding in studying alopecia, scientists have uncovered an unexpected link between T cells and hair growth, which could potentially be used to treat the condition. The findings, published in Nature Immunology, describe how regulatory T cells interact with skin cells using a hormone as a messenger to generate new hair follicles and hair growth.

Alopecia is an autoimmune condition where the immune system attacks the hair follicles, resulting in hair loss.

“For the longest time, regulatory T cells have been studied for how they decrease excessive immune reactions in autoimmune diseases,” explained Ye Zheng, associate professor at the Salk Institute and the paper’s corresponding author. “Now we’ve identified the upstream hormonal signal and downstream growth factor that actually promote hair growth and regeneration completely separate from suppressing immune response.”

Initially, the researchers were investigating the roles of regulatory T (Treg) cells and glucocorticoid hormones in autoimmune diseases. (Glucocorticoid hormones are cholesterol-derived steroid hormones produced by the adrenal gland and other tissues.) They first investigated how these immune components functioned in multiple sclerosis, Crohn’s disease and asthma.

They found that glucocorticoids and Treg cells did not function together to play a significant role in any of these conditions. So, they thought they’d have more luck looking at environments where Treg cells expressed particularly high levels of glucocorticoid receptors (which respond to glucocorticoid hormones), such as in skin tissue. The scientists induced hair loss in normal mice and mice lacking glucocorticoid receptors in their Treg cells.

“After two weeks, we saw a noticeable difference between the mice — the normal mice grew back their hair, but the mice without glucocorticoid receptors barely could,” says first author Zhi Liu, a postdoctoral fellow in Associate Prof Zheng’s lab. “It was very striking, and it showed us the right direction for moving forward.”

The findings suggested that some sort of communication must be occurring between Treg cells and hair follicle stem cells to allow for hair regeneration.

The scientists then investigated how the regulatory T cells and glucocorticoid receptors behaved in skin tissue samples, and found that glucocorticoids instruct the Treg cells to activate hair follicle stem cells, leading to hair growth. This crosstalk between the T cells and the stem cells depends on a mechanism whereby glucocorticoid receptors induce production of the protein TGF-beta3, all within the regulatory T cells. TGF-beta3 then activates the hair follicle stem cells to differentiate into new hair follicles, promoting hair growth. Additional analysis confirmed that this pathway was completely independent of regulatory T cells’ ability to maintain immune balance.

However, Treg cells don’t normally produce TGF-beta3, as they did here. A database search revaled that this phenomenon occurs in injured muscle and heart tissue, similar to how hair removal simulated a skin tissue injury in this study.

“In acute cases of alopecia, immune cells attack the skin tissue, causing hair loss. The usual remedy is to use glucocorticoids to inhibit the immune reaction in the skin, so they don’t keep attacking the hair follicles,” said Associate Prof Zheng. “Applying glucocorticoids has the double benefit of triggering the regulatory T cells in the skin to produce TGF-beta3, stimulating the activation of the hair follicle stem cells.”

This study revealed that Treg cells and glucocorticoid hormones are not just immunosuppressants but also have a regenerative function. Next, the scientists will look at other injury models and isolate Treg cells from injured tissues to monitor increased levels of TGF-beta3 and other growth factors.

Source: Salk Institute

Categories : Immune System Mental HealthTags :

Autoimmune Clue in Some Schizophrenia Cases

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Mirror symbolising schizophrenia
Source: Vince Fleming on Unsplash

Schizophrenia, which affects how people interact with reality, is difficult to treat because it has many possible causes. In a study published in Cell Reports Medicine, Japanese researchers have identified an autoantibody – an antibody which attacks the body’s own tissues – in some patients with schizophrenia.

Notably, they also found that this autoantibody caused schizophrenia-like behaviours and changes in the brain when they injected it into mice.

When considering possible autoantibodies that might cause schizophrenia, researchers from Tokyo Medical and Dental University (TMDU) had a specific protein in mind. Previous research has suggested that neural cell adhesion molecule (NCAM1), which helps facilitate synaptic connections, may have a role in the development of schizophrenia.

“We decided to look for autoantibodies against NCAM1 in around 200 healthy controls and 200 patients with schizophrenia,” explained lead author of the study Hiroki Shiwaku. “We only found these autoantibodies in 12 patients, suggesting that they may be associated with the disorder in just a small subset of schizophrenia cases.”

The research went on to find out whether these autoantibodies could cause any changes that commonly occur in schizophrenia, so they purified autoantibodies from some of the patients and injected them into the brains of mice.

“The results were impressive,” said the study’s senior author, Hidehiko Takahashi. “Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behaviour and synapses that were similar to what is seen in humans with schizophrenia.”

The mice given the patient autoantibodies had cognitive impairment and changes in their regulation of the startle reflex, which are both seen in other animal models of schizophrenia. They also had fewer synapses and dendritic spines, which are structures that are important for the connections between brain cells, and are also affected in schizophrenia.

The study findings hold promise for the diagnosis and treatment of schizophrenia can present very differently among patients and is often resistant to treatment. If schizophrenia is indeed caused by autoantibodies against NCAM1 in some patients, this will lead to important improvements in their diagnosis and treatment.

Source: Tokyo Medical and Dental University

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T Cells Need a Break, Too

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T cell
Scanning Electron Micrograph image of a human T cell. Credit: NIH/NIAID

While T cells are the body’s warriors against infection, without rest and maintenance T cells can die, leaving their hosts more susceptible to pathogens, researchers reported in the journal Science.

“We may have to change how we teach T cell biology,” said Professor Lieping Chen, who is the senior author of the study.

T cells remain in a quiescent state until pathogens are detected, but the molecular mechanisms of this state were previously unknown.

In the new study, researchers showed that a protein known as CD8a – which is found in a subset of T cells called CD8 cells – is crucial to keeping the cells in this dormant state. When scientists deleted this protein in mice, the protective CD8 cells were unable to enter a quiescent state and died, leaving the host vulnerable to infections.

Further, they identified another protein, PILRa, that provides a biochemical signal to CD8a. By disrupting this protein pair, both “memory” CD8 cells – previously been exposed to pathogens – and naïve cells died because they lacked the ability to stay in a quiescent state.

The researchers hope that understanding why this resting state is crucial to maintenance and survival of T cells can lead to improved immune system function.

Chen noted that as people age they tend to lose both naïve and memory T cells, making older individuals more susceptible to infections. It is possible that the inability of T cells to remain in a quiescent state could lead to people becoming more susceptible to infections and cancer, the authors suggest.

Source: Yale University

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Hypoxia can Trigger Immune System Reaction

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Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

New research from scientists at La Jolla Institute for Immunology (LJI), shows that hypoxia can activate the same group of immune cells that cause inflammation during asthma attacks. During hypoxia, these cells flood the airways with lung-damaging molecules.

Hypoxia is a known trigger for developing and worsening lung conditions such as severe asthma, chronic obstructive pulmonary disease (COPD), and fibrosis. To treat and prevent these diseases, researchers need to understand why a lack of oxygen would affect the immune system.

“We show how lack of oxygen can be part of a feedback loop that can contribute to even worse inflammation,” says LJI Professor and Chief Scientific Officer Mitchell Kronenberg, PhD, a member of the LJI Center for Autoimmunity and Inflammation. “This work gives us insight into the causes of fibrosis of the lung and severe asthma.”

Prof Kronenberg and colleagues worked with a genetically altered mouse model to mimic the signals of hypoxia in the airway’s epithelial cells, which line the paths to the lungs. They discovered that combining the hypoxia signals with inflammatory signals stimulated the “innate,” or rapidly responding immunity, and an immune cell type called an ILC2.

An ILC2’s job is to make signaling molecules – cytokines – that quickly alert other immune cells to react to a pathogen. Unfortunately, ILC2s sometimes over-react and respond to harmless environmental allergens. In these cases, ILC2s churn out cytokines that drive mucus production and inflammation in the lungs. All this swelling and mucus leads to hypoxia.

As they report in Journal of Experimental Medicine, ILC2s respond to hypoxia as well, adding to the lung damage already caused during an asthma attack.

“That hypoxia may then contribute further to inflammation,” said Prof Kronenberg.

The next step was to figure out exactly how epithelial cells activate ILC2 during hypoxia. LJI Postdoctoral Fellow Jihye Han, PhD, led the work to uncover an unexpected culprit: adrenomedullin (ADM). ADM is known for its role in helping blood vessels dilate, but until now it had no known role in immune function.

Prof Kronenberg was surprised to see ADM involved — but not shocked. “We’re finding that many molecules with no previously known role in the immune system can also be important for immune function,” said Prof Kronenberg. “We need to understand that more generally.”

The researchers showed that human lung epithelial cells exposed to hypoxia also produced ADM. This means ADM or its receptor could be targets for treating inflammatory and allergic lung diseases.

The challenge is to find a balance between dampening the harmful immune response without leaving the body vulnerable to infections. Prof Kronenberg points out that the epithelial cell-ADM-ILC2 connection protected mice from hookworm infections, which damage the lungs and gut.

“ADM is a new target for lung diseases and has been implicated in bacterial pneumonia as well,” said Prof Kronenberg. “But blocking it would have to be done carefully.”

Source: La Jolla Institute for Immunology

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B Cells Play a Surprising Role in Bone Marrow Output

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Scanning electron micrograph image of a human B cell. Credit: NIH/NIAID

New research in Nature Immunology has found that B cells play a surprising role in increasing or decreasing the bone marrow’s output of white blood cells. The findings may lead to new treatments for conditions that arise when white blood cell production goes out of balance.

Professor Matthias Nahrendorf, senior author of the study, explained that the nervous system plays a role in controlling blood cell production through neurotransmitters. “This is for instance important in people exposed to stress, where stress hormones — part of the ‘fight-or-flight’ response controlled by the sympathetic nervous system — may increase bone marrow activity and cardiovascular inflammation in response to the neurotransmitter noradrenaline,” he said. The parasympathetic nerves on the other hand, slow down responses and bring about a state of calm to the body, mainly through the neurotransmitter acetylcholine.

Because acetylcholine can have a protective effect against inflammation and heart disease, the researchers studied this neurotransmitter in the bone marrow. “When we looked into how acetylcholine acts on the production of blood cells, we found that it does the expected — it reduces white blood cells, as opposed to noradrenaline, which increases them,” said Prof Nahrendorf. “What was unexpected though was the source of the neurotransmitter acetylcholine.”

In the bone marrow, the typical nerve fibres that are known to release acetylcholine were not found. Instead, it was the antibody-producing B cells supplied the acetylcholine in the bone marrow. “Thus, B cells counter inflammation — even in the heart and the arteries — via dampening white blood cell production in the bone marrow. Surprisingly, they use a neurotransmitter to do so,” said Prof Nahrendorf.

Tapping into this process may help investigators develop strategies to block inflammation in cardiovascular conditions such as atherosclerosis. “Ultimately this may lead to new therapeutics that combat myocardial infarction, stroke, and heart failure,” said Prof Nahrendorf.

Source: Massachusetts General Hospital

Categories : Immune System Injury & TraumaTags :

Researchers Identify a Key Regulatory Mechanism in Inflammation

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Firefighter
Source: Pixabay CC0

A newly published study has identified a key regulatory mechanism in inflammation that may lead to new targets for resolving that inflammation –and the inflammation of patients with sepsis, cancer and COVID.

In the journal PNAS, scientists reported their discovery of a regulatory pathway for immune response after infection or injury, such as burns. Dysregulation of this pathway could differentiate those who are at risk of fatal sepsis or help identify targets to resolve this unregulated inflammation.

“We are very excited about the findings in this paper and the far-reaching impacts it could have on understanding a key regulatory step in the immune response,” said co-lead author Cindy McReynolds, who holds a doctorate in pharmacology and toxicology.

In a rodent model, the research team found that the metabolites of linoleic acid formed by the enzyme, soluble epoxide hydrolase (sEH), drive damaging inflammation after injury. These metabolites, known as lipid mediators, regulate inflammation, blood pressure and pain. Drugs that inhibit the sEH enzyme and reduce inflammation could lead to better outcomes.

“Our previous work identified that these same lipid mediators were up-regulated in severe COVID infections, and we are now finding that these compounds play a role in modulating the immune response so that the body is unable to fight infection or respond properly to trauma without leading to a potentially fatal overreaction,” said Dr McReynolds.

“This dysregulation has fatal consequences in serious diseases such as COVID, cancer, sepsis, burn, where fatality rates can be as high as 40 percent in severe cases,” she said. “An understanding of these pathways can help identify patients at risk of developing serious disease or identify new therapeutic targets for treatment.”

“The immunological disbalance we see in many cases of severe burn injury, trauma and sepsis pose a huge clinical challenge as we lack the understanding of how to diagnose and treat it,” explained co-lead author Dr Christian Bergmann. “With this work, we reveal an important mechanism how immune cells are functionally disabled by sEH-derived metabolites of linoleic acid.”

“The natural compounds we are studying in this paper are metabolites of linoleic acid (LA), an essential fatty acid the body needs in very small amounts to survive and is only available through the diet,” Dr McReynolds elaborated. “At lower concentrations, these metabolites are necessary for regulating thermogenesis and heart health but promote inflammation at higher concentrations. LA is more stable and much cheaper than longer chain polyunsaturated fatty acids, so heavily processed foods have higher LA content to increase shelf-life. Additionally, agricultural practices, such as feeding animals corn-based diets, have increased LA in meats and dairy products.”

“As a result, we are consuming the highest amount of linoleic acid and have the highest recorded concentration of LA in our fatty tissue in human history,” McReynolds said. “As our bodies respond to stress or disease, we metabolise LA into the regulatory metabolites that were monitored in this paper. At higher concentrations, the immune system was unable to properly respond to infection, thereby promoting a sustained immune response. These observations are important in inflammatory-driven diseases, such as sepsis and COVID, but could also be important in understanding many of the increased chronic diseases we are seeing in our population.”

Source: UC Davis

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Meat, Gut Bacteria and Multiple Sclerosis

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Gut microbiome. Credit: Darryl Leja, NIH

There appears to be a link between eating meat, gut bacteria and multiple sclerosis, according to new research published in EBioMedicine. The study teased out subtle connections that could lead to a better understanding of the causes of the disease.

The autoimmune disease multiple sclerosis (MS) is more prevalent in specific regions, particularly the northern mid-latitudes, suggesting that geography is somehow linked to the disease, perhaps involving diet. However, the exact relationships between diet, immune response, and MS has been a mystery. What exactly triggers the body to attack the myelin sheaths in MS in the first place is unknown.

Growing evidence suggests that bacteria might play a role. Gut bacteria affect the immune system, and diet affects the gut. Researchers studied the gut microbiome, immune systems, diet, and blood metabolites in 25 MS patients and 24 healthy controls to look for any subtle but important correlations.

“We found a number of gut bacteria associated with MS and severity of disability of MS patients,” said Dr Yanjiao Zhou. “We also found increased autoimmune markers and signature metabolites in MS. But what is really interesting is how these systems connect with each other, and how diet is involved in these connections. Using multi-OMICS approaches, we try to close the loop and show the associations between multiple systems.”

Meat eating was the strongest link in their analysis, where higher meat consumption saw a decrease in the population of Bacteroides thetaiotaomicron, a bacteria associated with digesting carbohydrates from vegetables.

Higher meat consumption, seen in the MS patients, was also linked to an increase in T-helper 17 cells in the immune system, and an increase in S-adenosyl-L-methionine (SAM) in their blood.

Meat eating was not a predictor of MS. But the evidence suggested that, in MS, something causes gut bacteria to disassociate with the immune system, leading to heightened T-helper 17 cells and autoimmune attacks on the nervous system. And it tends to be associated with eating meat.

Future research aims to recruit more volunteers, including those with more severe MS. Eventually they hope to understand more of the cause-and-effect between diet, bacterial ecosystems in the gut, and immune response, and potentially help prevent or mitigate MS symptoms in people suffering from the disease.

Source: University of Connecticut