Category: Immune System

Differences in Influenza Responses According to Genetic Ancestries

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Researchers have uncovered differences in immune pathway activation to influenza infection between individuals of European and African genetic ancestry, according to a study published in Science. Many of the genes that were associated with these immune response differences to influenza are also enriched among genes associated with COVID disease severity. 

“The lab has been interested in understanding how individuals from diverse populations respond differently to infectious diseases,” said first author Haley Randolph, a graduate student at the University of Chicago. “In this study, we wanted to look at the differences in how various cell types respond to viral infection.”

The researchers examined gene expression patterns in peripheral mononuclear blood cells, a diverse set of specialised immune cells that play important roles in the body’s response to infection. These cells were gathered from men of European and African ancestry and then exposed the cells to flu in a laboratory setting. This let the team examine the gene signatures of a variety of immune cell types, and observe how the flu virus affected each cell type’s gene expression.

The results showed that individuals of European ancestry showed an increase in type I interferon pathway activity during early influenza infection.

“Interferons are proteins that are critical for fighting viral infections,” said senior author Luis Barreiro, PhD, Associate Professor of Medicine at UChicago. “In COVID-19, for example, the type I interferon response has been associated with differences in the severity of the disease.”

This increased pathway activation hindered the replication of the virus more and limited viral replication later on. “Inducing a strong type I interferon pathway response early upon infection stops the virus from replicating and may therefore have a direct impact on the body’s ability to control the virus,” said Barreiro. “Unexpectedly, this central pathway to our defense against viruses appears to be amongst the most divergent between individuals from African and European ancestry.”

The researchers saw a variety of differences in gene expression across different cell types, suggesting a constellation of cells that work together to fight disease.

Such a difference in immune pathway activation could explain influenza outcome disparities between different racial groups; Non-Hispanic Black Americans are more likely to be hospitalised due to the flu than any other racial group.

However, these results are not evidence for genetic differences in disease susceptibility, the researchers point out. Rather, possible differences in environmental and lifestyle between racial groups could be influencing gene expression, and affecting the immune response.

“There’s a strong relationship between the interferon response and the proportion of the genome that is of African ancestry, which might make you think it’s genetic, but it’s not that simple,” said Barreiro. “Genetic ancestry also correlates with environmental differences. A lot of what we’re capturing could be the result of other disparities in our society, such as systemic racism and healthcare inequities. Although some of the differences we show in the paper can be linked to specific genetic variation, showing that genetics do play some role, such genetic differences are not enough to fully explain the differences in the interferon response.”

These differences in viral susceptibility may not be confined to just influenza. Comparing a list of genes associated with differences in COVID severity, the researchers found that many of the same genes showed significant differences in their expression after flu infection between individuals of African and European ancestry.

“We didn’t study COVID patient samples as part of this study, but the overlap between these gene sets suggests that there may be some underlying biological differences, influenced by genetic ancestry and environmental effects, that might explain the disparities we see in COVID outcomes,” said Barreiro.

As they explore this further, the researchers hope to figure out which factors contribute to the differences in the interferon response, and immune responses more broadly, to better predict individual disease risk.

Source: EurekAlert!

Effective Psoriasis Treatment Could be a ‘TWEAK’ Away

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A key protein called TWEAK damages skin cells in psoriasis patients, according to a new study in mice and with human skin cells, and targeting TWEAK may help control the disease.

Although there are effective treatments for psoriasis, an autoimmune disease that shows up as patches of red, inflamed skin and painful, scaly rashes, not everyone responds to these therapies – and for many, the relief is temporary.

“These therapies don’t reduce disease by 100 percent, and they don’t cure the disease” says La Jolla Institute for Immunology (LJI) Professor Michael Croft, PhD. “And if you take patients off those drugs, the disease almost always comes back.”

“We think TWEAK might be considered a potential target for the treatment of psoriasis,” said first author Rinkesh Gupta, PhD, a postdoctoral fellow at LJI. “It’s good to have this chance to develop a new therapeutic option.”

The findings build on the lab’s earlier research showing that TWEAK can interact with keratinocytes, the most common type of skin cell. By investigating TWEAK-deficient mice, the researchers found that TWEAK is a driver of inflammation in a model of psoriasis.
The new study, published in Science Immunology, shows that TWEAK does not work alone; it teams up with two other proteins, tumour necrosis factor (TNF) and interleukin-17 (IL-17), to trigger inflammation. These three seem to control inflammatory molecule production and the expression of additional inflammation-associated proteins in patients with psoriasis.

“The fact that they work together suggests the disease is essentially driven by all three of those particular proteins at the same time,” explained Prof Croft. “The primary implication is that TWEAK will also be a good drug target. as has already been proven for TNF and IL-17.”

The researchers tested this idea with a mouse model of psoriasis to compare how well a TWEAK-inhibitor measured up to therapies inhibiting IL-17 or TNF.

“If you inhibit TWEAK from working on its receptor on keratinocytes, you get the same therapeutic effect as when you inhibit TNF or IL-17,” said Dr Gupta. A particularly encouraging aspect of this finding since TNF and IL-17 are both FDA-approved drug targets for psoriasis.

Prof Croft thinks TWEAK inhibitors have potential as therapies for many types of skin diseases. “We think TWEAK is involved in skin inflammation in general,” he said.

His lab is now investigating the role of TWEAK in atopic dermatitis, and while a distinct disease from psoriasis, they do have a few things in common – and there are not as many good treatments for atopic dermatitis.

“There’s certainly a lot of room for improvement in treatment of atopic dermatitis patients,” he said.

Source: La Jolla Institute for Immunology

Immune Cells Persist 6 Months after COVID Vaccination

Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

A recent study shows that T helper cells produced by people who received either of the two available messenger RNA (mRNA) vaccines for COVID persist six months after vaccination, at only slightly reduced levels from two weeks after vaccination. They are also at significantly higher levels than in unvaccinated individuals.

In the study, published in Clinical Infectious Diseases, the researchers also found that the T cells they studied recognise and help protect against the highly infectious delta variant of SARS-CoV-2.

“Previous research has suggested that humoral immune response – where the immune system circulates virus-neutralising antibodies – can drop off at six months after vaccination, whereas our study indicates that cellular immunity – where the immune system directly attacks infected cells – remains strong,” said Professor Joel Blankson, MD, PhD, study senior author. “The persistence of these vaccine-elicited T cells, along with the fact that they’re active against the delta variant, has important implications for guiding COVID vaccine development and determining the need for COVID boosters in the future.”

The researchers sampled blood from 15 study participants at three times: prior to vaccination, between seven and 14 days after their second Pfizer/BioNTech or Moderna vaccine dose, and six months after vaccination. The median age of the participants was 41 and none had evidence of prior SARS-CoV-2 infection.

CD4+ T lymphocytes are nicknamed helper T cells because they assist another type of immune system cell, the B lymphocyte (B cell), to respond to antigens on viruses such as SARS-CoV-2. Activated by the CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark infected cells for disposal from the body or memory cells that ‘remember’ the antigen’s biochemical structure for a faster response to future infections. Therefore, a CD4+ T cell response can serve as a measure of how well the immune system responds to a vaccine and yields humoral immunity.

The researchers found that the number of helper T cells recognising SARS-CoV-2 spike proteins was very low pre-vaccination, with a median of 2.7 spot-forming units (SFUs, the level of which is a measure of T cell frequency) per million peripheral blood mononuclear cells (PBMCs, identified as any blood cell with a round nucleus, including lymphocytes). Between 7 and 14 days after vaccination, the T cell frequency rose to a median of 237 SFUs per million PBMCs. At six months after vaccination, the level dropped slightly to a median of 122 SFUs per million PBMCs – a T cell frequency still significantly higher than before vaccination.

Six months after vaccination, the number of T cells recognising the delta variant spike protein was not significantly different from that of T cells attuned to the original virus strain’s protein.

“The robust expansion of T cells in response to stimulation with spike proteins is certainly indicated, supporting the need for more study to show booster shots do successfully increase the frequency of SARS-CoV-2-specific T cells circulating in the blood,” said Prof Blankson. “The added bonus is finding that this response also is likely strong for the delta variant.”

Source: John Hopkins Medicine

A Key Immune Function in Red Blood Cells Has Been Discovered

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Red blood cells have been discovered to have a critical function as immune sensors by binding cell-free DNA (nucleic acid) present in the body’s circulation during sepsis and COVID. 

This DNA-binding capability triggers their removal from circulation, driving inflammation and anaemia during severe illness and playing a much larger role in the immune system than previously thought. Scientists have long known that red blood cells also interacted with the immune system, but not whether they directly altered inflammation, until now. The study appears in Science Translational Medicine.

“Anaemia is common, affecting about a quarter of the world’s population. Acute inflammatory anaemia is often seen early after an infection such as parasitic infections that cause malaria,” said senior author Nilam Mangalmurti, MD, an assistant professor of Medicine at Penn. “For a long time we haven’t known why people, when they are critically ill from sepsis, trauma, COVID, a bacterial infection, or parasite infection, develop an acute anaemia. These findings explain one of the mechanisms for the development of acute inflammatory anaemia for the first time.”

Toll-like receptors (TLRs) play a key role in the immune system by activating immune responses like cytokine production. Analysing the red blood cells of about 50 sepsis patients and 100 COVID patients the study found that, during these illnesses, red blood cells express more TLR9 on their surface.

When the red blood cells bind too much inflammation-causing nucleic acid, they lose their normal structure, causing the body to no longer recognise them, prompting macrophages to engulf them. When this happens, it causes the immune system to become activated in otherwise unaffected organs, creating inflammation. The discovery of this mechanism will allow research on blocking this specific receptor and creating targeted therapies for autoimmune diseases, infectious diseases, and various inflammatory illnesses associated with acute anaemia.

“Right now when patients in the ICU become anaemic, which is almost all of our critically ill patients, the standard is to give them blood transfusions, which has long been known to be accompanied by a host of issues including acute lung injury and increased risk of death,” Prof Mangalmurti said. “Now that we know more about the mechanism of anaemia, it allows us to look at new therapies for treating acute inflammatory anaemia without transfusions, such as blocking TLR9 on the red blood cells. Targeting this TLR9 may also be a way to dampen some of the innate immune activation without blocking this receptor in immune cells, which are very important for the host when fighting a pathogen or injury.”

This DNA-binding discovery could also have implications for research into using red blood cells in diagnostics, Prof Mangalmurti said. For example, a physician might be able to take red blood cells from a patient with pneumonia, sequence the nucleic acid absorbed from the infection, and identify the specific kind of pathogen to better determine what kind of antibiotic to prescribe.

Prof Mangalmurti and colleagues are looking at whether this is a valid option in diagnosing infection in critically ill patients and if this DNA-binding mechanism by red blood cells is a universal mechanism of anaemia in parasitic infections.

Source: Perelman School of Medicine at the University of Pennsylvania

Differences in Natural and Vaccine-induced COVID Immunity Revealed

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A new study recently published in Nature has found that immune protection resulting from COVID protection creates lasting effects in memory B cells.

Unlike circulating antibodies, which peak soon after vaccination or infection only to fade a few months later, memory B cells can remain to ward off severe disease for decades. They also evolve over time, learning to produce successively more potent ‘memory antibodies’ that are more effective at neutralising the virus and with better adaptation to variants.

Though vaccination instils higher levels of circulating antibodies than natural infection, the study suggests that not all memory B cells are created equal. While vaccination gives rise to memory B cells that evolve over a few weeks, natural infection births memory B cells that continue to evolve over several months, producing highly potent antibodies adept at eliminating even viral variants.

Though the findings suggest an advantage from natural infection over vaccination, this does not outweigh the dangers of illness and death from COVID, the researchers warn.

“While a natural infection may induce maturation of antibodies with broader activity than a vaccine does – a natural infection can also kill you,” explained Professor Michel C. Nussenzweig, head of Rockefeller’s Laboratory of Molecular Immunology. “A vaccine won’t do that and, in fact, protects against the risk of serious illness or death from infection.”

When any virus enters the body, immune cells immediately release circulating antibodies, which decay at variable rates depending on the vaccine or infection. They may confer protection for months or years but then dwindle in number, allowing possible reinfection.

Long term protection is provided by memory B cells that produce memory antibodies. Studies suggest that memory B cells for smallpox last at least 60 years after vaccination; those for Spanish flu, nearly a century. And while memory B cells don’t necessarily block reinfection, they can prevent severe disease.

Recent studies have suggested that within five months of receiving a vaccine or recovering from a natural infection, some no longer retain sufficient circulating antibodies to keep the novel coronavirus at bay, but memory B cells remain vigilant. Until now, however, scientists did not know whether the vaccines could be expected to provide the sort of robust memory B cell response seen after natural infection.

Prof Nussenzweig and colleagues resolved to tease out any differences in memory B cell evolution by comparing blood samples from convalescent COVID patients to those from never-infected mRNA-vaccinated individuals.

Vaccination and natural infection elicited similar numbers of memory B cells, which rapidly evolved between the first and second dose of the Pfizer and Moderna vaccines, producing increasingly potent memory antibodies. But after two months, progress stalled. The memory B cells were present in large numbers and expressed potent antibodies, but the antibodies were not getting any stronger. Also, although some of these antibodies were able to neutralize Delta and other variants, there was no overall improvement in breadth.

The researchers found that in convalescent patients, however, memory B cells continued to evolve and improve up to one year after infection. With every memory B cell update, more potent and more broadly neutralising memory antibodies were coming out.

There are several potential reasons that memory B cells produced by natural infection might be expected to outperform those produced by mRNA vaccines, the researchers said.

It is possible that the body responds differently to viruses that enter through the respiratory tract than those that are injected. Or perhaps an intact virus goads the immune system in a way the vaccines’ spike protein antigens simply cannot. It may also be possible that the virus persists in the naturally infected for weeks, giving the body more time to mount a robust response. The vaccine, on the other hand, is flushed out of the body mere days after triggering the desired immune response.

Memory B cells appear to undergo limited bouts of evolution in response to mRNA vaccines, a finding which may have significant implications for booster shots. A booster with the current mRNA vaccine would likely stimulate memory cells to produce antibodies strongly protective against the original virus and somewhat less so against the variants, Prof Nussenzweig said.

“When to administer the booster depends on the object of boosting,” he said. “If the goal is to prevent infection, then boosting will need to be done after 6 to 18 months depending on the immune status of the individual. If the goal is to prevent serious disease, boosting may not be necessary for years.”

Source: Rockefeller University

How Vitamin A Enters into Gut Immune Cells

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Researchers have reported in Science how vitamin A enters immune cells in the intestines – findings that could offer insight to treat digestive diseases and perhaps help improve the efficacy of certain vaccines.

“Now that we know more about this important aspect of immune function, we may eventually be able to manipulate how vitamin A is delivered to the immune system for disease treatment or prevention,” said Lora Hooper, PhD, Chair of Immunology at UT Southwestern, Howard Hughes Medical Institute Investigator.

Vitamin A is a fat-soluble nutrient which is converted to retinol and then to retinoic acid before it is used. It is important for every tissue in the body, said Dr. Hooper, Professor of Immunology, Microbiology, and in the Center for the Genetics of Host Defense at UT Southwestern. It is particularly crucial for the adaptive immune system, a subset of the broader immune system that reacts to specific pathogens based on immunological memory, the type formed by exposure to disease or vaccines.

Although researchers knew that some intestinal immune cells called myeloid cells can convert retinol to retinoic acid, how they acquire retinol to perform this task was a mystery, said Dr. Hooper, whose lab investigates how resident intestinal bacteria influence the biology of humans and other mammalian hosts.

Lead author Ye-Ji Bang, PhD, a postdoctoral fellow in the Hooper Lab, and colleagues focused on serum amyloid A proteins, a family of retinol-binding proteins that some organs produce during infections. They used biochemical techniques to determine which cell surface proteins they attached to, and identified LDL receptor-related protein 1 (LRP1).

Drs. Bang, Hooper, Herz, and colleagues showed that LRP1 was present on intestinal myeloid cells, where it seemed to be transferring retinol inside. When the researchers deleted the gene for this receptor in mice, preventing their myeloid cells from taking up the vitamin A derivative, the adaptive immune system in their gut virtually disappeared, said Dr Hooper. T and B cells and the molecule immunoglobulin A, critical components of adaptive immunity, were significantly reduced. Researchers then compared the response to Salmonella infection between mice with LRP1 and those without. Those without the receptor quickly succumbed to the infection.

The findings suggest that LRP1 is what conveys retinol into myeloid cells. If a way could be developed to inhibit this process, explained Dr Hooper, it could calm down the immune response in inflammatory diseases that affect the intestines, such as inflammatory bowel disease and Crohn’s disease. Alternatively, boosting LRP1 activity could boost immune activity, making oral vaccines more effective.

Source: UT Southwestern Medical Center

Almost ‘Superhuman’ Immune Response Found in Certain People

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A series of studies in recent months has found that, thanks to the mRNA vaccine and previous infection, some people mount an extraordinarily powerful immune response against SARS-CoV-2 which some scientists have referred to as ‘superhuman’.

Called ‘hybrid immunity’, their bodies produce very high levels of antibodies, with great flexibility: likely capable of fighting off the SARS-CoV-2 variants currently circulating but also likely effective against future variants.

“Overall, hybrid immunity to SARS-CoV-2 appears to be impressively potent,” Crotty wrote in commentary in Science published in June.

“One could reasonably predict that these people will be quite well protected against most  and perhaps all of — the SARS-CoV-2 variants that we are likely to see in the foreseeable future,” says Paul Bieniasz, a virologist at Rockefeller University who helped lead several of the studies.

Bieniasz and his colleagues found antibodies in these individuals capable of strongly neutralising the six variants of concern tested, including Delta and Beta, as well as several other viruses related to SARS-CoV-2, including SARS-CoV-1.

“This is being a bit more speculative, but I would also suspect that they would have some degree of protection against the SARS-like viruses that have yet to infect humans,” Bieniasz said.

People who have had a ‘hybrid’ exposure to the virus, were infected with it in 2020 and then immunised with mRNA vaccines this year. “Those people have amazing responses to the vaccine,” said virologist Theodora Hatziioannou at Rockefeller University, who also helped lead several of the studies. “I think they are in the best position to fight the virus. The antibodies in these people’s blood can even neutralize SARS-CoV-1, the first coronavirus, which emerged 20 years ago. That virus is very, very different from SARS-CoV-2.”

These antibodies were so effective they were even able to deactivate a virus purposefully engineered to be highly resistant to neutralisation, containing 20 mutations that are known to prevent SARS-CoV-2 antibodies from binding to it. Antibodies from those who were only vaccinated or who only had prior coronavirus infections were ineffecgtive against this engineered virus..

This shows how powerful the mRNA vaccine can be in those infected with SARS-CoV-2, she said. “There’s a lot of research now focused on finding a pan-coronavirus vaccine that would protect against all future variants. Our findings tell you that we already have it.

The catch is getting COVID. “After natural infections, the antibodies seem to evolve and become not only more potent but also broader. They become more resistant to mutations within the [virus].”

Hatziioannou and colleagues don’t know if this applies to all those mRNA-vaccinated and previously COVID-infected. “We’ve only studied the phenomena with a few patients because it’s extremely laborious and difficult research to do,” she said.
“With every single one of the patients we studied, we saw the same thing.” The study reports data on 14 patients.

Several other studies lend credence to her hypothesis and reinforce the idea that exposure to both a coronavirus and an mRNA vaccine triggers an exceptionally powerful immune response. In one study in NEJM, scientists analysed antibodies generated by people who had been infected with SARS-CoV-1 back in 2002 or 2003 and who then received an mRNA vaccine this year.

Remarkably, these people also produced high levels of antibodies that could neutralise a whole range of variants and SARS-like viruses. Many questions remain, such as the effect of a third booster shot, or being infected again.

“I’m pretty certain that a third shot will help a person’s antibodies evolve even further, and perhaps they will acquire some breadth [or flexibility], but whether they will ever manage to get the breadth that you see following natural infection, that’s unclear.”

Immunologist John Wherry, at the University of Pennsylvania, is a bit more hopeful. “In our research, we already see some of this antibody evolution happening in people who are just vaccinated,” he said, “although it probably happens faster in people who have been infected.”

In a recent study, Wherry and colleagues showed that, over time, uninfected people with only two doses of the vaccine begin to produce more flexible antibodies, so a third dose would give even more of an evolutionary boost to the antibodies, Wherry said. So a person will be better equipped to fight off whatever variant the virus puts out there next.

“Based on all these findings, it looks like the immune system is eventually going to have the edge over this virus,” said Bieniasz, of Rockefeller University. “And if we’re lucky, SARS-CoV-2 will eventually fall into that category of viruses that gives us only a mild cold.”

Source: NPR

Degree of Platelet Drop, Not Count, Important in Sepsis Mortality

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Mortality risk in sepsis is linked to the degree of platelet reduction, rather than absolute platelet count, according to new Japanese research.

Sepsis, a potentially life-threatening condition, arises from tissue and organ damage from an overactive infection response. Sepsis is commonly characterised by abnormally low platelet counts, which is believed to be associated with its high mortality rate.

Recently, Nagoya University researchers and colleagues have shown that a high degree of platelet reduction, rather than an abnormally low platelet count, raises mortality risks in sepsis. The findings, recently presented in the journal Scientific Reports, could lead to the development of precise and preventive treatments for sepsis-associated coagulopathy.

It is known that during sepsis, disseminated intravascular coagulation (DIC) forms tiny blood clots throughout the bloodstream, depleting platelets. Based on this, the international criterion for the diagnosis of sepsis-associated DIC uses platelet count and trials have been done using this criterion. However, very few trials have led to the development of effective treatments for sepsis-associated DIC.

There is however a different theory, that degree of platelet depletion (a rapid drop), rather than the absolute platelet count, accounts for much mortality risk in sepsis-associated DIC. But since there is little evidence for this theory, it has not been considered an international criterion for the disease prognosis.

With this in mind, researchers conducted a study to examine the significance of the degree of platelet reduction on sepsis mortality rate, using data from 200 859 sepsis patients staying in intensive care units of 208 US hospitals.

Corresponding author Dr Daisuke Kasugai of the Nagoya University Hospital, said: “To our knowledge, it was the largest study to evaluate the prognostic impact of both the degree of platelet depletion and absolute platelet counts in patients with sepsis.”

The degree of platelet reductions was found to be associated with the mortality risk associated with sepsis, regardless of absolute platelet count, indicating higher mortality risk with a fast decrease in platelet count. Dr Kasugai said:  “Surprisingly, we also found that if the platelet count decreases by 11% or more, the risks of bleeding, as well as thrombosis development (a serious condition caused by the formation of blood clots in blood vessels or the heart), increases.”

The researchers therefore concluded that, compared to the absolute platelet count, the degree of platelet reduction could be a more plausible criterion for assessing the mortality risk of the sepsis-associated DIC. They hope that this study will lead to effective treatments for sepsis-associated DIC.

Source: Nagoya University

Metabolic Changes in Plasma, Immune Cells Linked to COVID Severity

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Analysing plasma from patients infected with SARS-CoV-2, researchers have uncovered underlying metabolic changes that regulate how immune cells react to COVID, these are associated with disease severity and could be used to predict patient survival. The findings were published in the journal Nature Biotechnology.

“We know that there are a range of immune responses to COVID, and the biological processes underlying those responses are not well understood,” said co-first author Jihoon Lee, a graduate student at Fred Hutchinson Cancer Research Center. “We analyzed thousands of biological markers linked to metabolic pathways that underlie the immune system and found some clues as to what immune-metabolic changes may be pivotal in severe disease. Our hope is that these observations of immune function will help others piece together the body’s response to COVID. The deeper understanding gained here may eventually lead to better therapies that can more precisely target the most problematic immune or metabolic changes.”

The researchers performed two draws on each of nearly 200 patients during the first week after being diagnosed with SARS-CoV-2 infection, and analysed their plasma and single immune cells. The analysis included 1387 genes involved in metabolic pathways and 1050 plasma metabolites.

Increased COVID severity was found to be associated with metabolite alterations, which suggests increased immune-related activity. In addition, each major immune cell type was found to have a distinct metabolic signature.

“We have found metabolic reprogramming that is highly specific to individual immune cell classes (eg “killer” CD8+ T cells, “helper” CD4+ T cells, antibody-secreting B cells, etc.) and even cell subtypes, and the complex metabolic reprogramming of the immune system is associated with the plasma global metabolome and are predictive of disease severity and even patient death,” said co-first and co-corresponding author Dr. Yapeng Su, a research scientist at Institute for Systems Biology. “Such deep and clinically relevant insights on sophisticated metabolic reprogramming within our heterogeneous immune systems are otherwise impossible to gain without advanced single-cell multi-omic analysis.”

“This work provides significant insights for developing more effective treatments against COVID. It also represents a major technological hurdle,” said Dr. Jim Heath, president and professor of ISB and co-corresponding author on the paper. “Many of the data sets that are collected from these patients tend to measure very different aspects of the disease, and are analysed in isolation. Of course, one would like these different views to contribute to an overall picture of the patient. The approach described here allows for the sum of the different data sets to be much greater than the parts, and provides for a much richer interpretation of the disease.”

Source: Max Planck Institute

Traitorous Immune Cells Explain Why the Elderly Feel the Cold

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In a new study, Yale researchers found that the immune cells within fat that are designed to burn calories to protect us from cold temperatures start to turn against us as we age, making the elderly more vulnerable to the cold.

The study, published in Cell Metabolism, found that the fat tissue of older mice loses the immune cell group 2 innate lymphoid cells (ILC2) which restore body heat in cold temperatures. However, trying to stimulate production of new ILC2 cells in aging mice actually makes them more prone to cold-induced death, showing how difficult it is to solve aging-related problems.

“What is good for you when you are young, can become detrimental to you as you age,” said Vishwa Deep Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology and co-corresponding author of the study.

Prof Dixit and former colleague Emily Goldberg, now an assistant professor at UCSF, were curious about why there are immune cells in fat tissue, as they are usually concentrated in pathogen-exposed areas like nasal passages, lungs, and skin. When they sequenced genes from cells of old and young mice they found that older animals lacked ILC2 cells, a deficit which limited their ability to burn fat in cold conditions.

When they introduced a molecule that boosts the production of ILC2 in aging mice, the immune system cells were restored but the mice were surprisingly even less tolerant of cold temperatures.

“The simple assumption is that if we restore something that is lost, then we are also going to restore life back to normal,” Dixit said. “But that is not what happened. Instead of expanding healthy cells of youth, the growth factor ended up multiplying the bad ILC2 cells that remained in fat of old mice.”

However, when ILC2 cells were taken from younger mice and transplanted into older mice, the older animals’ cold tolerance was restored.

“Immune cells play a role beyond just pathogen defense and help maintain normal metabolic functions of life,” Dixit said. “With age, the immune system has already changed and we need to be careful how we manipulate it to restore the health of the elderly.”

Source: SciTech Daily