Stories about: immunology

A new tactic for antibiotic-resistant pneumonia: Making neutrophils stronger, but fewer in number

bacterial pneumonia with neutrophils

Antibiotic resistance is a growing threat in bacterial pneumonia. While treatments that stimulate the immune system can help the body fight the invaders, these treatments can also cause inflammation that damages and weakens lung tissue.

Now, research in Science Translational Medicine suggests a way to have the best of both worlds: enhanced bacterial killing with reduced inflammation.

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Could poop transplants treat peanut allergy? A clinical trial begins

FMT peanut allergy

Increasing evidence supports the idea that the bacteria living in our intestines early in life help shape our immune systems. Factors like cesarean birth, early antibiotics, having pets, number of siblings and formula feeding (rather than breastfeeding) may affect our microbial makeup, or microbiota, and may also affect our likelihood of developing allergies.

Could giving an allergic person the microbiota of a non-allergic person prevent allergic reactions? In a new clinical trial, a team led by Rima Rachid, MD, of Boston Children’s Division of Allergy and Immunology, is testing this idea in adults with severe peanut allergies. The microbiota will be delivered through fecal transplants — in the form of frozen, encapsulated poop pills.

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This autoimmune awareness month, meet Boston scientists who are pushing the envelope in autoimmune research

“Red” and “green” B cells emerge from the pack as best producers of the potent autoantibodies in a mouse model of the autoimmune disease known as lupus.
In a mouse model of lupus, colorized red and green B cells outdo their blue, yellow and aqua competitors. Each color represents a different B cell clone. The proliferation of red and green B cells demonstrates that these clones have emerged as the best producers of autoantibodies. Credit: Michael Carroll lab (Boston Children’s Hospital/Harvard Medical School)

The basic biological mechanisms that underpin autoimmune disorders are finally coming to light. Researchers in Boston’s Longwood medical area — a neighborhood where the streets are flanked by hospitals, research institutions and academic centers — are setting the stage for a new wave of future therapies that can prevent, reduce or even reverse symptoms of disease.

Inside the lab of Michael Carroll, PhD, scientists are working to understand how and why immune cells start to attack the body’s own tissues; it turns out the immune system’s B cells compete with each other in true Darwinian fashion. On the way to this discovery, the lab has flushed out new potential drug targets that could ease autoimmune symptoms — or stop them entirely — by “resetting” the body’s tolerance to itself.

Carroll’s team has also drawn some of the first links between chronic inflammation, synapse loss and neuropsychiatric disease in lupus.

The implications for a link between inflammation and synapse loss go beyond lupus because inflammation underpins so many diseases and conditions, ranging from Alzheimer’s to viral infection and even to to chronic stress. In which case, are we all losing synapses to some varying degree? Carroll plans to find out.

Meanwhile, Sun Hur, PhD, and members of her lab are digging deep on a genetic variant and its link to pediatric inflammatory autoimmune disorders like Aicardi-Goutieres syndrome.

“We’ve found that chronic inflammation and autoinflammatory disorders can originate from genetic mutations to MDA5 that cause it to misrecognize ‘self’ as ‘non-self,’ essentially launching the immune system into self-attack mode,” said Hur.

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A new tactic for eczema? A newly identified brake on the allergic attack

baby with eczema
(Arkady Chubykin/Adobe Stock)

Eczema affects about 17 percent of children in developed countries. Often, it’s a gateway to food allergy and asthma, initiating an “atopic march” toward broader allergic sensitization. There are treatments – steroid creams and a recently approved biologic – but they are expensive or have side effects. A new study in Science Immunology suggests a different approach to eczema, one that stimulates a natural brake on the allergic attack.

The skin inflammation of eczema is known to be driven by “type 2” immune responses. These are led by activated T helper 2 (TH2) cells and type 2 innate lymphoid cells (ILC2s), together known as effector cells. Another group of T cells, known as regulatory T cells or Tregs, are known to temper type 2 responses, thereby suppressing the allergic response.

Yet, if you examine an eczema lesion, the numbers of Tregs are unchanged. Interestingly, Tregs comprise only about 5 percent of the body’s T cells, but up to 50 percent of T cells in the skin.

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Single-shot protection? Building a better hepatitis B vaccine for newborns

newborn vaccines
(Illustrations: Elena Hartley)

The hepatitis B vaccine is one of only three vaccines that are routinely given to newborns in the first days of life. But the current hepatitis B vaccine has limitations: multiple “booster” doses are needed, and it can’t be given to premature babies weighing less than 2 kg.

Annette Scheid, MD, a neonatologist at Brigham and Women’s Hospital, is interested in leveraging infant immune differences to create a better hepatitis B vaccine for newborns. “The reality is that we have to vaccinate several times,” she says. “But we all dream of a vaccine that you give only once.”

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Link found between chronic inflammation, autoimmune disorders and “false alarms”

Viruses (pictured here) have a genetic signature that a receptor called MDA5 recognizes. But when MDA5 confuses the body's own genetic material with that of a virus, disease ensues.
Viruses have a genetic signature that a human receptor called MDA5 recognizes, causing the immune system to attack. But when MDA5 confuses the body’s own genetic material for that of a virus, disease ensues.

The human body’s innate immune system employs a variety of “sensors” for identifying foreign invaders such as viruses. One such viral sensor is a receptor called MDA5, found in every cell of the body.

Inside each cell, MDA5 constantly scans genetic material, checking if it’s native to the body or not. As soon as MDA5 identifies the genetic signature of a viral invader, it trips a system-wide alarm, triggering a cascade of immune activity to neutralize the threat.

But if a genetic mutation to MDA5 causes it to confuse some of the body’s own genetic material for being foreign, “false alarms” can lead to unchecked inflammation and disease. Scientists from Boston Children’s Hospital have discovered a new link between MDA5’s ability to discriminate between “self” and “non-self” genetic material — called RNA duplexes — and a spectrum of autoimmune disorders.

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Science and medicine in 2018: What’s the forecast?

2018 predictions for biomedicine

Vector consulted its many informants to find out which way the wind will blow in 2018. Here are their predictions for what to expect in genetics, stem cell research, immunology and more.

GENETICS

Gene-based therapies mature

We will continue to see successes in 2018 reflecting the maturation of gene therapy as a viable, generalizable platform for curing many rare diseases. Also, we will see exciting new applications of other maturing platforms, like CRISPR/Cas9 gene editing and oligonucleotide therapies for neurologic diseases, building on the success of nusinersen for spinal muscular atrophy.

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How do cells release IL-1? The answer packs a punch, and could enable better vaccines

In hyperactivated immune cells, gasdermin D punches holes in the cell membrane that let IL-1 out — without killing the cell.

Interleukin-1 (IL-1), first described in 1984, is the original, highly potent member of the large family of cellular signaling molecules called cytokines that regulate immune responses and inflammation. It’s a key part of our immune response to infections, and also plays a role in autoimmune and inflammatory diseases. Several widely used anti-inflammatory drugs, such as anakinra, block IL-1 to treat rheumatoid arthritis, systemic inflammatory diseases, gout and atherosclerosis. IL-1 is also a target of interest in Alzheimer’s disease.

Yet until now, no one knew how IL-1 gets released by our immune cells.

“Most proteins have a secretion signal that causes them to leave the cell,” says Jonathan Kagan, PhD, an immunology researcher in Boston Children’s Hospital’s Division of Gastroenterology. “IL-1 doesn’t have that signal. Many people have championed the idea that IL-1 is passively released from dead cells: you just die and dump everything outside.”

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Breastfeeding protects against food allergy: We have evidence

Mother breastfeeding her baby. Is she helping her child avoid food allergy?

Eating allergenic foods during pregnancy can protect your child from food allergies, especially if you breastfeed, suggests new research. The findings, in a mouse model of allergy, underscore recent advice that pregnant or nursing mothers not avoid allergenic foods like eggs and peanuts.

The study is the first controlled investigation to demonstrate protection against food allergy from breast milk, while also pointing to a biological mechanism for inducing food tolerance. It was published online today in the Journal of Experimental Medicine.

“Whether mothers should eat allergenic foods during pregnancy or avoid them has been controversial,” says Michiko Oyoshi, PhD, of Boston Children’s Division of Allergy and Immunology, who led the study in collaboration with Richard Blumberg, MD, of Brigham and Women’s Hospital, her co-senior author.

“Different studies have found different results, in part because it’s hard in human studies to know when mothers and babies first encountered a specific food,” says Oyoshi. “But in a mouse model, we can control exposure to food.”

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Pre-treated blood stem cells reverse type 1 diabetes in mice

autoimmune attack in type 1 diabetes
In type 1 diabetes, autoreactive T-cells (like the one in yellow) attack insulin-producing beta cells in the pancreas. What if blood stem cells could be taught to neutralize them? (Image: Andrea Panigada)

Type 1 diabetes is caused by an immune attack on the pancreatic beta cells that produce insulin. To curb the attack, some researchers have tried rebooting patients’ immune systems with an autologous bone-marrow transplant, infusing them with their own blood stem cells. But this method has had only partial success.

New research in today’s Science Translational Medicine suggests a reason why.

“We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease,” says Paolo Fiorina, MD, PhD, of Boston Children’s Hospital, senior investigator on the study.

But they also found that the defect can be fixed — by pre-treating the blood stem cells with small molecules or with gene therapy, to get them to make more of a protein called PD-L1.

In experiments, the treated stem cells homed to the pancreas and reversed hyperglycemia in diabetic mice, curing almost all of them of diabetes in the short term. One third maintained normal blood sugar levels for the duration of their lives.

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