Coronavirus Second Wave: Tips to Boost Your Immune System

Coronavirus Second Wave: Tips to Boost Your Immune System

  • April 9, 2021

New Delhi: We have been fighting the battle against COVID 19 for over a year now. It is crucial to boost our immune system, as it protects our body from harmful substances, germs, and cell changes that could make a person sick. Also Read – Uttar Pradesh: Night Curfew in Bareilly, Saharanpur From Today | Check Latest Guidelines Here

Rinki Kumari, Chief Dietician, Fortis Hospital, Bangalore shares a few tips to strengthen your immunity naturally: Also Read – Chhattisgarh: Raipur Under 10-day Lockdown From Today. Here’s What Allowed, What’s NOT

  • Good sleep is key: Getting enough sleep is important in maintaining a good immune system. When you are sick, simply getting adequate rest and sleep will naturally help to boost your immunity.
  • Maintain a healthy diet: It is important to maintain a good healthy diet to keep your immune system in check. One can include whole plant foods like fruits, vegetables, nuts, seeds, and legumes which are rich in nutrients and antioxidants that help fight against harmful pathogens. Healthy fats like those found in olive oils, salmon, etc have anti-inflammatory properties that help the body fight off disease-causing bacteria and viruses. It is crucial to avoid added sugars as they increase obesity, type 2 diabetes, heart risks to name a few, thus affecting the immune system.
  • Exercise regularly: Moderate exercise can reduce inflammation and promote the healthy turnover of immune cells. Exercising regularly helps in keeping the body and mind healthy.
  • Drink lots of water: Drinking water is crucial in keeping your body healthy. Dehydration can cause several problems like indigestion, headache, physical performance, kidney function issues, etc to name a few.
  • Manage your stress levels: Relieving stress and anxiety is key to immune health. Long-term stress promotes inflammation, as well as imbalances in immune cell function. Multiple methods can be adapted to lower stress levels, like yoga, meditation, dance, listening to soothing music to name a few.
  • Regular health checkups: It is important to invest time and money in regular health checkups. Health conditions like asthma, diabetes, cholesterol, health diseases, etc can affect the immune system and thereby increasing the chance of infections.

Also Read – Telangana Govt Tightens Rules Amid Rise in COVID-19 Cases, to Impose Rs 1000 Fine For Not Wearing Mask

Vitamin C Is Beneficial To Your Health

Vitamin C Is Beneficial To Your Health

  • April 8, 2021

Vitamin C is water-soluble and can be obtained from many fruits and vegetables, it is also an essential vitamin that the body is not able to produce, it has many roles and has been linked to some impressive health benefits.

While some take supplements to meet the daily requirements for vitamin C it is recommended to get your intake from food sources such as bell peppers, spinach, broccoli, kale, strawberries, kiwi, and oranges. 

Vitamin C is a potent antioxidant that can help to strengthen the body’s natural defenses by boosting the immune system by protecting cells from harmful free radical molecules that can accumulate and promote oxidative stress which is linked to many chronic diseases. Studies have shown that vitamin C can increase blood antioxidant levels by 30% helping the body’s natural defenses to fight inflammation and reduce the risk of chronic diseases. 

According to the CDC, around one-third of American adults have high blood pressure, putting them at risk for heart disease which is the leading cause of death around the globe. Studies have shown that vitamin C can help to lower blood pressure in those with and without high blood pressure. This may be done by helping the blood vessels to relax that carry blood from the heart which helps to reduce blood pressure levels. However, this does not mean that those with high blood pressure should rely on vitamin C to rely on vitamin C alone to manage high blood pressure. 

Research analyzing 9 studies found that those taking at least 700 mg a day of vitamin C had a 25% lower risk of heart disease than those who did not. Another analysis of 15 studies found that consuming vitamin C from foods and not supplements was linked to a lower risk of heart disease. Additionally, another analysis of 13 studies found that taking vitamin C supplements significantly reduced risk factors for heart disease including blood cholesterol and triglyceride levels. These studies suggest that at least 500 mg of vitamin C each day can help to reduce the risk of heart disease, however, if you are consuming a vitamin C-rich diet taking supplements may not provide additional heart health benefits. 

Studies suggest that vitamin C may help to reduce blood uric acid levels and help prevent gout attacks which is a type of arthritis that affects around 4% of American adults. 

Vitamin C helps to improve the absorption of iron from the diet and assists in converting iron that is poorly absorbed such as plant-based sources of iron and turns it into a form that is easier to absorb. This is especially important to those that are vegan as meat is a major source of iron, and iron is important to a variety of functions such as making red blood cells and transporting oxygen throughout the body. As a result, vitamin C may help to reduce the risk of anemia among those prone to iron deficiency. 

Vitamin C is involved in many parts of the immune system, helping to encourage the production of lymphocytes and phagocyte white blood cells that help to protect the body against infections. Vitamin C also helps these white blood cells function more effectively while protecting them from harmful free radicals. Vitamin C is actively transported to the skin where it is an antioxidant that also helps to strengthen the skin’s barriers and may help to shorten wound healing time. Vitamin C helps to boost immunity, and lower levels have been linked to poor health outcomes, such as those with pneumonia tend to have lower levels. 

Globally well over 35 million people are affected by dementia, studies suggest that inflammation and oxidative stress near the brain, spine, and nerves can increase the risk of dementia. Vitamin C is a potent antioxidant, lower levels of vitamin C have been linked to an impaired ability to think and remember. Studies have shown that those with dementia have lower blood levels of vitamin C, and a high intake of vitamin C from food/supplements have been shown to have a protective effect on thinking and memory as we age. Studies suggest that vitamin C might help protect against conditions such as dementia, and if you don’t get enough from your diet supplements might help. 

While vitamin C does afford many proven benefits, more research is needed on the effects on the nervous system. In addition to the proven benefits, vitamin C also has many unfounded claims supported by anecdotal evidence. The bottom line is that it has been linked to many impressive benefits such as boosting the immune system, increasing antioxidant levels, lowering blood pressure, improving iron absorption, protecting against gout attacks, and reducing the risk for heart disease and dementia. It is always best to get vitamin C from food sources, but if you are struggling to get enough from your diet a supplement may help (it is recommended to consult with your doctor or certified medical professional before taking any supplement). 

What To Eat Before And After Your COVID-19 Vaccine To Lessen Side Effects

What To Eat Before And After Your COVID-19 Vaccine To Lessen Side Effects

  • April 5, 2021

By May 1, all Americans will be eligible for a COVID-19 vaccine. Five states (Alaska, Arizona, Mississippi, Utah and West Virginia) have already opened vaccines to all adults over 16, with others planning to follow.

According to the Centers for Disease Control and Prevention, side effects of the vaccines can include pain, redness and swelling at the injection site, as well as possible fever, headache, tiredness, nausea, chills and muscle pain. These symptoms are actually a good sign that your body is building immunity, and they will usually pass in a few days (if they do not, call your doctor), the CDC advises.

But there are small steps you can take to lessen those side effects, and many of them have to do with your diet.

Helpful foods and beverages for dealing with vaccine side effects

Obviously, it’s not fun feeling under the weather for a few days, which is especially possible after your second dose of the Pfizer or Moderna vaccine. “Budget for adequate rest and sleep when taking the vaccine, and maybe going easy on exercise,” advises Dr. Ronald Hoffman, a New York City integrative physician. Beyond that, he said, there are some simple do’s and don’ts in terms of food and drink.

Do: Try ginger tea for nausea

Ginger has a reputation as an excellent and safe traditional remedy for gastrointestinal complaints. Ginger tea is easy to make, and a simple recipe can be found here.

Don’t: Fast or do anything “drastic like juicing or detox”

“The development of immunity depends on the body ‘reading’ instructions from the vaccine and synthesizing antibodies and white blood cells, which requires adequate protein in the diet,” Hoffman said.

Do: Hydrate with healthy fluids

From water to tea to your favorite flavored sparkling water, drink up. The fever a vaccine may induce can lead to dehydration.

The Mediterranean diet places an emphasis on healthy fats, such as those found in salmon.

The Mediterranean diet places an emphasis on healthy fats, such as those found in salmon.

Do: Eat a healthy, Mediterranean-style diet

Try to start eating especially healthy a few weeks ahead of your appointment for a vaccine. A Mediterranean-style diet is known to have anti-inflammatory effects, but it’ll take a few weeks to kick in.

“Preconditioning your body for a few weeks beforehand makes more sense than just being abstemious in the immediate aftermath of the shot,” Hoffman said.

The diet emphasizes vegetables, fruits, whole grains, healthy Omega-3 and monounsaturated fats (like those in olive oil), fish, poultry, beans and eggs. Dairy and red meat are limited. One study found that individuals over 65 years of age who ate five or more servings of fruit and vegetables per day had a stronger immune response to a pneumococcal vaccine than peers who ate two servings or fewer.

Do: Consider eating a low glycemic index diet for at least a few days after the vaccine

A low glycemic index diet will keep your blood sugar steady. Research centered around diabetes has shown that lower glucose levels tend to be anti-inflammatory. In general, foods that keep blood sugar at healthy levels include green vegetables, most beans, whole grains and multigrain breads, fruits like berries and apples, and of course healthy lean proteins, eggs and nuts.

Do: Turn to that favorite remedy of all time, chicken soup

A nice healing broth with many well-cooked veggies is easy to digest and nourishing.

Do: Fine-tune your gut health to increase your immune response

Across the human population, immune response to vaccines varies. Some of this depends on age — as we get older, our immunity wanes. Some of it depends on individual variation. And some of it depends on the type of vaccine you receive.

An important aspect of vaccine response, and of immunity in general, is a healthy gut microbiome, said Dr. Todd Born, a naturopathic physician and certified nutrition specialist in Washington. Not only are vaccine responses variable, but Born said that a healthy gut microbiome has been shown in scientific studies to increase immune response to vaccines.

“A diverse and healthy microbial community in the gut will influence the immune system directly,” Born told HuffPost.

Born recommends a high-fiber diet and fermented foods, and to “start two weeks before the vaccine and continue for a minimum of two weeks after.”

“Fiber-rich diets encourage the growth of beneficial bacteria that support the immune response,” he explained. And fermented foods ― from yogurt and kefir to kimchi and sauerkraut ― can help enhance the gut microbes that support immune response.

Studies have actually shown that some common probiotic organisms, such as lactobacillus rhamnosus, can improve the antibody response to vaccines. This and other healthy lactobacilli can be found in products in your supermarket ― these include kefir, yogurt, and some fermented beverages.

Born also likes a homemade “immune support” soup, which he often recommends to patients during cold and flu season. He recommended adding chopped onion and garlic, grated ginger, juice from half a lemon, fresh minced parsley and one grated carrot to a quart of miso, chicken or mushroom broth. Simmer for 15 minutes and add the parsley and lemon juice at the end.

While you sip that nourishing soup and let your immune system do its work, play some uplifting music and make a gratitude list. Thirty years of research has shown that stress, depression and loneliness can impair the immune system’s response to vaccines.

So, nourish your body with healthy food and drink, stay hydrated, rest well and be of good cheer. You’ll be giving your immune system the best chance to respond well to the vaccine and to recover quickly.

Should recovered patients get COVID-19 jab?

Should recovered patients get COVID-19 jab?

  • March 26, 2021

As COVID-19 vaccines become more and more available to the general public questions on who should get the jab also have been rising, most prominently whether people who have been infected with coronavirus should also be inoculated – most scientists agree that the answer is “yes.”

Regardless of previous infection, the United States Centers for Disease Control and Prevention says people should plan on getting vaccinated when it’s their turn. “It’s a pretty straightforward question,” Johns Hopkins infectious disease specialist Dr. Amesh Adalja told The Associated Press (AP). “Yes, you need to get vaccinated.”

Professor Mustafa Gerek from the University of Health Sciences told Demirören News Agency (DHA) that after infection “it is likely that you have enough antibodies at which stage you may not need vaccination” but it is unclear how long immunity lasts.

After someone recovers, their immune system should keep them from becoming sick again right away. “Your immune system is able to identify the virus, and protect itself,” said Dr. Saskia Popescu, an infectious disease expert at George Mason University.

Scientists still do not know exactly how long this immunity lasts or how strong it is, though recent research suggests the protection could last for several months.

It’s impossible to know how long a person might be immune, said Dr. Prathit Kulkarni, an infectious disease expert at Baylor College of Medicine. “There’s no way to calculate that.”

Vaccines, by contrast, are designed to bring about a more consistent and optimal immune response. They also should boost whatever preexisting immunity a person might have from an infection, experts say.

The Turkish Health Ministry, on its COVID-19 information platform, lists health care workers who previously had the infection as eligible for the vaccine one month after they have suffered from the coronavirus, as they are considered the highest risk group. Other risk groups can, and are encouraged to, be vaccinated six months after infection.

“Since we’re in this pandemic, and don’t have a handle on it, the safer approach is to vaccinate,” Kulkarni said. “You don’t lose anything and you stand to benefit.”

If you have been infected in the last three months, the U.S. Centers for Disease Control and Prevention (CDC) says vaccination can be delayed if you want to let others go first while supplies are limited.

“All things being equal you would want the person with no protection to go first,” Adalja said.

Immunai acquires single-cell data developer Dropprint Genomics to build out its immune system atlas

Immunai acquires single-cell data developer Dropprint Genomics to build out its immune system atlas

  • March 25, 2021

Shortly after raising $60 million to fuel its artificial intelligence work, aimed at digitally charting the human body’s immune system, Immunai announced it has acquired the single-cell sequencing software startup Dropprint Genomics.

Previously backed by Y Combinator, the San Francisco-based Dropprint aims to provide big data and machine learning solutions to help crunch the numbers taken from millions of separate immune system cells.

Immunai, meanwhile, launched less than one year ago with a $20 million seed round, after being founded by researchers and computer engineers from MIT, Harvard and Stanford University.

Now, with February’s series A fundraising—co-led by Schusterman Family Investments, Duquesne Family Office, Catalio Capital Management and Dexcel Pharma, plus backing from Viola Ventures and TLV Partners—Immunai aims to expand its Annotated Multi-omic Immune Cell Atlas, or AMICA, which characterizes individual cells at a high resolution.

“The immune system is implicated in nearly every illness, making our technology critical for identifying, diagnosing, and treating disease, from cancer and infectious disease to autoimmune disorders,” Immunai co-founder and CEO Noam Solomon said at the time. 

“Since Immunai’s founding in 2018, we have been mapping the immune system through observational genomics, using multi-omic single-cell technologies and machine learning to better understand how the immune system operates,” Solomon added. “Our expansion into functional genomics will help our partners tackle their most pressing questions in therapy development and will ultimately improve the lives of many patients.”

Dropprint’s own database of immune cells will be folded into AMICA, including samples taken from patients with cancer and autoimmune diseases. 

Meanwhile, the company’s co-founders, Meena Subramanian and Rachel Gate, will join Immunai’s machine learning and computational biology team. The financial terms of the deal were not disclosed.

In addition, Immunai has expanded its senior leadership. Peter Smibert, former director of technology innovation at the New York Genome Center, will serve as VP of functional genomics. MD Anderson Cancer Center’s Alexandria Cogdill will become director of business development while Adeeb Rahman was named senior director of single-cell immunology, after heading up technology development at the Human Immune Monitoring Center at Mount Sinai’s Icahn School of Medicine.

Finally, Immunai’s scientific co-founder, Danny Wells, will become senior VP of strategic research. Wells previously helped lead reverse translational medicine at the Parker Institute for Cancer Immunotherapy.

Repurposed heart and flu drugs that protect platelets improve survival of septic mice

Repurposed heart and flu drugs that protect platelets improve survival of septic mice

  • March 25, 2021

Despite continued improvements in antibiotics and hospital intensive care, staph sepsis -; a bloodstream infection caused by Staphylococcus aureus bacteria -; still causes severe illness or death in 20 to 30 percent of patients who contract it.

Rather than continue to throw more antibiotics at the problem, University of California San Diego researchers want to boost the other side of the equation: the patient’s own immune system.

The team recently discovered a battle that occurs between staph bacteria and platelets -; blood cells known better for their role in clotting than in immune defense. In some sepsis cases, they found, the bacteria win out and platelet levels plummet. Patients with fewer platelets were more likely to die of staph sepsis than patients with higher platelet counts.

The researchers also determined that two currently available prescription medications, approved by the U.S. Food and Drug Administration (FDA) for other uses, protect platelets and improve survival in mouse models of staph sepsis. The two repurposed drugs were ticagrelor (Brilinta), a blood thinner commonly prescribed to prevent heart attack recurrence, and oseltamivir (Tamiflu), prescribed to treat the flu.

The study publishes March 24, 2021 in Science Translational Medicine.

In many cases, the antibiotics we give these patients should be able to kill the bacteria, based on lab tests, yet a significant number of patients are not pulling through. If we can reduce mortality in staph sepsis by 10 or 20 percent by arming or protecting the immune system, we can likely save more lives than discovering an additional new antibiotic that may still not cure the sickest patients.”


Victor Nizet, MD, Senior Author, Distinguished Professor at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences

The study started with a group of 49 University of Wisconsin patients with staph sepsis. The team collected the patients’ blood, bacteria samples, and demographic and health information. To their surprise, it wasn’t white blood cell counts (immune cells) that correlated with patient outcomes -; it was the platelet count. Low platelet counts, defined in this case as fewer than 100,000 per mm3 blood, were associated with increased risk of death from staph sepsis. Approximately 31 percent of patients with low platelet counts died from the infection, compared to less than 6 percent of patients with platelets above the threshold.

In laboratory experiments, the researchers worked out what’s likely happening: Platelets secrete antimicrobial peptides that help the immune system destroy staph bacteria. At the same time, staph release an alpha-toxin that’s detrimental to platelets. In addition to poking holes in platelets, the bacteria’s alpha-toxin convinces the blood cells to produce an enzyme that trims off sugar molecules that decorate their own surfaces. The platelet’s new look is recognized by another molecule in the liver called the Ashwell-Morell receptor, which pulls “bald” platelets out of circulation.

Once Nizet and team had an idea of what might be happening in the patients who are less likely to survive staph sepsis, they turned to mouse models of the disease to find ways to tip the balance of what they call the “toxin-platelet-receptor” axis back in favor of the human patient.

The researchers tested several classes of drugs known to be safe in humans and known to act on platelets. Most drugs they tested had no effect, but two drugs made a big difference. Ticagrelor blocks staph’s alpha-toxin so it can’t injure platelets or stimulate its sugar-removing enzyme. Oseltamivir inhibits the platelet sugar-removing enzyme so the cells don’t go bald and aren’t cleared by the liver, even when staph’s alpha-toxin is around.

Mice with staph sepsis and treated with either ticagrelor or oseltamivir maintained more platelets and had less bacteria in their blood. Ultimately, approximately 60 percent of treated mice survived 10 days following infection, compared to 20 percent of untreated mice.

Side effects of these medications may include nausea, diarrhea and nosebleeds, and ticagrelor may cause uncontrollable bleeding. While new clinical trials specifically designed to test the drugs’ safety and efficacy for patients with staph sepsis would be ideal, Nizet said there’s little financial incentive for pharmaceutical companies to do so with an already profitable drug.

Still, repurposing commercially available drugs has many advantages.

“Discovering a new drug is tremendously expensive and takes many, many years,” said Nizet, who is also faculty lead for the Collaborative to Halt Antibiotic-Resistant Microbes (CHARM) at UC San Diego. “But if we look around at what we already have, what we already know to be safe, we may find many opportunities to improve patient outcomes.”

Sepsis can be caused by several types of bacteria in addition to staph, including Streptococcus pyogenes, Klebsiella, E. coli and Pseudomonas aeruginosa. According to the Centers for Disease Control and Prevention, each year at least 1.7 million adults in the U.S. develop sepsis and nearly 270,000 die as a result. One in three patients who die in a hospital has sepsis. And it’s one of the costliest of all diseases -; in 2013, for example, the Department of Health and Human Services reported that sepsis management added up to more than $24 billion in hospital expenses, or 13 percent of total U.S. hospital costs.

Source:

Journal reference:

Sun, J., et al. (2021) Repurposed drugs block toxin-driven platelet clearance by the hepatic Ashwell-Morell receptor to clear Staphylococcus aureus bacteremia. Science Translational Medicine. doi.org/10.1126/scitranslmed.abd6737.

Sargramostim drug can also improve memory in people with mild-to-moderate Alzheimer's disease

Sargramostim drug can also improve memory in people with mild-to-moderate Alzheimer’s disease

  • March 24, 2021

A new study suggests that Sargramostim, a medication often used to boost white blood cells after cancer treatments, is also effective in treating and improving memory in people with mild-to-moderate Alzheimer’s disease. This medication comprises of a natural human protein produced by recombinant DNA technology (yeast-derived rhu GM-CSF/Leukine®).

The study, from the University of Colorado Alzheimer’s and Cognition Center at the University of Colorado Anschutz Medical Campus (CU Anschutz), presents evidence from their clinical trial that shows that Sargramostim may have both disease-modifying and cognition-enhancing activities in Alzheimer’s disease patients. It was published online today by Alzheimer’s & Dementia: Translational Research and Clinical Interventions, an open access journal of the Alzheimer’s Association.

“The goal of the clinical trial was to examine the impact of a natural human protein called granulocyte-macrophage colony stimulating factor (GM-CSF) on people living with Alzheimer’s disease. We tested GM-CSF because people with rheumatoid arthritis tend not to get Alzheimer’s disease and we had previously found this protein, which is increased in the blood of people with rheumatoid arthritis, reduced amyloid deposition in Alzheimer’s mice and returned their poor memory to normal after a few weeks of treatment. Thus, naturally increased levels of GM-CSF in people with rheumatoid arthritis may be one reason that they are protected from Alzheimer’s disease,” said Huntington Potter, PhD, director of the CU Alzheimer’s and Cognition Center, who together with Jonathan Woodcock, Timothy Boyd and collaborators carried out the new trial.

“Human GM-CSF is the active compound in the known human drug Sargramostim, and we are the first to study its effect on people with Alzheimer’s disease.”

GM-CSF/Sargramostim is used to stimulate the bone marrow to make more white blood cells of a particular kind called macrophages and granulocytes, as well as progenitor cells that repair blood vessels. These white blood cells circulate throughout the body and remove cells, bacteria and amyloid deposits that aren’t supposed to be there, as well as promoting repair to damaged blood vessels and to the brain.

The researchers carried out a randomized, double-blind, placebo-controlled phase II trial to test the safety and efficacy of Sargramostim treatment in participants with mild-moderate Alzheimer’s disease.

Study participants who met eligibility criteria were randomized to receive injections of either Sargramostim (20 participants took a standard FDA dosage 250 mcg/m2/day subcutaneous injection for five days a week for three weeks) or placebo (20 participants took saline for five days a week for three weeks). The majority of the participants from the study were recruited and treated at CU Anschutz with a few from the University of South Florida.

The CU Anschutz researchers then conducted and studied multiple neurological, neuropsychological, cell, cytokine, Alzheimer’s pathology biomarkers and neuroimaging assessments.

They found that short-term Sargramostim treatment increased innate and other immune cells, modulated cytokine measures, and was safe and well-tolerated by participants. They also found cognition memory improved by almost two points in the 30 point Mini-Mental State Exam. Measures of blood biomarkers of Alzheimer’s disease–brain amyloid, tangles, and neurodegeneration–all improved toward normal.

These results suggest that short-term Sargramostim treatment leads to innate immune system activation, cognition and memory improvement, and partial normalization of blood measures of amyloid and tau pathology and neuronal damage in participants with mild-to-moderate Alzheimer’s disease.


This surprising finding that stimulating the innate immune system and modulating inflammation may be a new treatment approach and induced us to start a larger trial of Sargramostim in Alzheimer’s disease with more participants treated over a longer time.”


Huntington Potter, PhD, Director of CU Alzheimer’s and Cognition Center

This new trial will be funded by the Alzheimer’s Association/Part The Cloud, the University of Colorado, the Global Down Syndrome Foundation and by a large grant recently awarded from the National Institute on Aging.

Iron-binder DFX improves the effect of new TB antimicrobial, research shows

Iron-binder DFX improves the effect of new TB antimicrobial, research shows

  • March 23, 2021

Although Tuberculosis, or TB, killed nearly as many people as COVID-19 (approx. 1.8 million) in 2020, it did not receive as much media and public attention. The pandemic has proven that transmissible infection is indeed a global issue. TB remains a serious public health concern in Ireland, particularly with the presence of multi-drug resistant types and the numbers of complex cases here continuing to rise, with cases numbering over 300 annually.

Science tells us that iron is crucial for daily human function, but it is also an essential element for the survival of viruses and bacteria. For some time, scientists have known that depriving infections of iron can limit bacterial burden and help improve patient outcomes. Now scientists at Trinity College and St James’s Hospital have recently applied such a trick (of binding iron to support the immune system) to the treatment of TB, along with a new TB antimicrobial called Bedaquiline. The findings have been published (Thursday, 18th March 2021) in the prestigious journal, the International Journal of Molecular Sciences: https://bit.ly/3bXNBcd .The research is led by Professor Joseph Keane and Dr James Phelan.

Bedaquiline has been in use for less than 10 years for multi-drug resistant TB, yet last year Ireland saw its first case of TB that was Bedaquiline-resistant. We know that even as new antituberculosis drugs are introduced, the TB bacteria will become increasingly resistant.

For some time, Dr Phelan has been looking at how to support the immune system to improve treatment effectiveness. He has previously demonstrated how an iron-binding drug, called Desferrioxamine, or DFX, supports lung immunity against TB infection by driving the activation of a key metabolic pathway called ‘glycolysis’. The process of glycolysis helps immune cells make energy to fight infection which in turn drives several signals that improve the patient macrophages’ (white blood cells) ability to address TB infection. Recent data has shown that a large fraction of people suffering from TB lack this glycolytic response. DFX could compensate for this metabolic defect.

As an extension of this work, the research team has now demonstrated that immune macrophage cells infected with TB bacteria, and treated with the drug Bedaquiline, do a better job of killing the bacteria, if they are also treated with this iron-binder DFX. In addition, this approach also drives a panel of cytokines, or immune messengers, that could also help the macrophages to eliminate the pathogen.

The use of these antimicrobials has been the mainstay for TB treatment for almost half a century now; now is the time to make these antimicrobials function better for the patient. DFX, and other iron binders, could be one of the answers to this. The use of iron binders could help pave the way for the development of new host-directed-therapies; instead of targeting the pathogen, host-directed-therapies directly target infected cells and help them kill the pathogen. Therefore, the use host-directed-therapies as a treatment strategy could drastically improve the treatment and clinical care for patients suffering with tuberculosis and other devastating infectious diseases”.


Dr James Phelan, Department of Clinical Medicine, Trinity College and Study Senior Author

Source:

Journal reference:

Cahill, C., et al. (2021) The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG. International Journal of Molecular Sciences. doi.org/10.3390/ijms22062938.

Bacteria residing within tumor cells can boost cancer immunotherapy

Bacteria residing within tumor cells can boost cancer immunotherapy

  • March 22, 2021

Cancer immunotherapy may get a boost from an unexpected direction: bacteria residing within tumor cells. In a new study published in Nature, researchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system “sees” these bacteria and shown they can be harnessed to provoke an immune reaction against the tumor.

The study may also help clarify the connection between immunotherapy and the gut microbiome, explaining the findings of previous research that the microbiome affects the success of immunotherapy.

Immunotherapy treatments of the past decade or so have dramatically improved recovery rates from certain cancers, particularly malignant melanoma; but in melanoma, they still work in only about 40% of the cases.

Prof. Yardena Samuels of Weizmann’s Molecular Cell Biology Department studies molecular “signposts” – protein fragments, or peptides, on the cell surface – that mark cancer cells as foreign and may therefore serve as potential added targets for immunotherapy. In the new study, she and colleagues extended their search for new cancer signposts to those bacteria known to colonize tumors.

Using methods developed by departmental colleague Dr. Ravid Straussman, who was one of the first to reveal the nature of the bacterial “guests” in cancer cells, Samuels and her team, led by Dr. Shelly Kalaora and Adi Nagler (joint co-first authors), analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. They obtained bacterial genomic profiles of these tumors and then applied an approach known as HLA-peptidomics to identify tumor peptides that can be recognized by the immune system.

The research was conducted in collaboration with Dr. Jennifer A. Wargo of the University of Texas MD Anderson Cancer Center, Houston, Texas; Prof Scott N. Peterson of Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Prof Eytan Ruppin of the National Cancer Institute, USA; Prof Arie Admon of the Technion – Israel Institute of Technology and other scientists.

The HLA peptidomics analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. The crucial new finding was that the peptides were displayed on the cancer cell surfaces by HLA protein complexes – complexes that are present on the membranes of all cells in our body and play a role in regulating the immune response.

One of the HLA’s jobs is to sound an alarm about anything that’s foreign by “presenting” foreign peptides to the immune system so that immune T cells can “see” them. “Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner,” Kalaora says. “This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials.”

It’s unclear why cancer cells should perform a seemingly suicidal act of this sort: presenting bacterial peptides to the immune system, which can respond by destroying these cells. But whatever the reason, the fact that malignant cells do display these peptides in such a manner reveals an entirely new type of interaction between the immune system and the tumor.

This revelation supplies a potential explanation for how the gut microbiome affects immunotherapy. Some of the bacteria the team identified were known gut microbes. The presentation of the bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides enhance that immune response, enabling physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.

Moreover, the fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. “Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation,” Nagler says.

In a series of continuing experiments, Samuels and colleagues incubated T cells from melanoma patients in a laboratory dish together with bacterial peptides derived from tumor cells of the same patient. The result: T cells were activated specifically toward the bacterial peptides.

Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy. They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs.”


Yardena Samuels, Professor, Molecular Cell Biology Department, Weizmann Institute of Science

Freiburg researchers receive ERC funding to develop and test immunostimulatory drug candidates

New study shows how the immune system relates to cancer

  • March 22, 2021

Three University of Colorado Cancer Center researchers are part of a team that recently published a paper offering new insight into how the immune system relates to cancer. Quentin Vicens, PhD, Jeffrey Kieft, PhD, and Beat Vögeli, PhD, are authors on the paper, which looks at how an enzyme called ADAR1 operates in pathways associated with cancer.

“In a cell, ADAR1 edits native RNA — or self-RNA — so that the cell recognizes it as its own. It’s a key protection against autoimmune disorders,” Kieft says. “But if a virus infects, viral RNA isn’t edited by ADAR1, so the cell can recognize that and react. The cell knows it has foreign RNA, and it activates immune responses to fight off that infection.”

For their paper published last month in the journal Nature Communications, Kieft, Vögeli, Vicens, and the rest of the team — including Parker Nichols, a graduate student in the Structural Biology and Biochemistry program in the CU School of Medicine who works jointly in the Kieft and Vögeli labs — looked at where specifically the ADAR1 binds to RNA to perform the editing process. They already knew a domain of ADAR1 known as Z-alpha binds to a form of RNA called Z-RNA, but they found that Z-alpha ADAR1 can bind to other RNA forms as well.

The team asked, ‘How are all these locations in RNA being recognized by Z-alpha if they supposedly don’t form Z-RNA? One of the take-home messages is that other forms of RNA can bind to Z-alpha ADAR1 and can even partially form Z-RNA. That was a surprise because it shows that RNA can form this specific Z structure in places we didn’t recognize before.”


Jeffrey Kieft, PhD, Study Author, CU School of Medicine

The team is now proposing a model for how Z-alpha ADAR1 is able to bind to different types of RNA. It’s an important finding in cancer research because of the role of ADAR1 in cancer regulation. A normally functioning immune system oftentimes can detect cancerous cells as being dangerous and then eliminate them, but if there’s too much ADAR1 editing happening, a cell could be tamping down the immune response in an effort to protect itself.

“In a lot of cancers, there is upregulation of ADAR1; it is doing more than it should,” Kieft says. “The excess ADAR1 presumably is leading to more RNA editing than is normal. This is going to misregulate things, affecting specific regions of RNA or types of RNA.

The excess editing is going to throw off the normal immune response, but it probably has a lot of other affects in the cell as well. Cancer is a disease where gene regulation has gone awry, so if an important regulatory pathway like editing by ADAR has gone haywire, that can contribute to the cancer.”

Knowing all the targets of ADAR1 in a cell is also a step toward more effective therapies, Kieft says. If researchers understand the pathways, they may be able to find a way to disrupt the overactive editing process and boost the immune response. It’s a finding applicable to many other diseases as well — Vögeli says since the paper was published, the researchers have heard from other scientists around the country interested in ADAR1.

“We have gotten a lot of feedback on the paper,” he says. “There is a lot of interest in this field right now, and other people are interested in how they could use our structural information.”

Vögeli and Vicens are now organizing a meeting focused on ADAR1 function and putting together special issues of the journals Molecules and International Journal of Molecular Sciences.

Vicens says the research project also illustrates the importance of collaborative work and being open to new directions. “I basically brought a new project and direction to the Kieft lab when I joined,” Vicens says. “Both labs were open to supporting it intellectually and financially, and the resultant team effort enabled research that would not otherwise have been done.”

Source:

Journal reference:

Nichols, P. J., et al. (2021) Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions. Nature Communications. doi.org/10.1038/s41467-021-21039-0.

capsimmunesystem.org