Stories about: Division of Infectious Diseases

Our intestinal microbiome influences metabolism — through the immune system

microbiome metabolism concept - in Drosophila. In absence of intestinal bacteria to modulate metabolism, flies develop fat droplets.

Research tells us that the “good” bacteria that inhabit our intestines help to regulate our metabolism. A new study in fruit flies shows one of the ways in which these commensal microbes keep us metabolically fit.

The findings, published today in Cell Metabolism, suggest that innate immune pathways, our first line of defense against bacterial infection, have a side job that’s equally important.

The intestine’s digestive cells use an innate immune pathway to respond to harmful bacteria by producing antimicrobial peptides. But other intestinal cells, enteroendocrine cells, use the same pathway, known as IMD, to respond to “good” bacteria — by fine-tuning body metabolism to diet and intestinal conditions.

“What’s most interesting to me is that some innate immune pathways aren’t just for innate immunity,” says Paula Watnick, MD, PhD, of the Division of Infectious Diseases at Boston Children’s Hospital. “Innate immune pathways are also listening to the ‘good’ bacteria – and responding metabolically.”

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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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Science Seen: Tackling S. aureus by eavesdropping on infections

S. aureus vaccine messenger RNA transcriptome
This messenger RNA ‘heat map,’ generated from 50 patient samples, shows potential target proteins for a more effective S. aureus vaccine. The color scale indicates the magnitude of the transcription level, with red highest.

Staphylococcus aureus causes 11,000 deaths annually in the U.S. alone and is frequently antibiotic-resistant. It’s a leading cause of pneumonia, bloodstream infections, bone/joint infections and surgical site infections and the #1 cause of skin and soft tissue infections. Efforts to develop an S. aureus vaccine have so far failed: the vaccines don’t seem to be capturing the right ingredients to make people immune.

Kristin Moffitt, MD, in Boston Children’s Hospital’s Division of Infectious Diseases, took a step back and asked: “What proteins does S. aureus need to make to establish infection?” The answer, she reasoned, could point to new antigens to include in a vaccine.

The above image shows an early result from Moffitt’s investigation. It’s a “heat map” of the messenger RNA signature — a snapshot of the proteins S. aureus is potentially up-regulating during infection.

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Strengthening newborns’ immune systems: A secret in the plasma

Blood cells
The immunosuppressant effect in newborns’ blood comes not from blood cells themselves, but from the plasma that surrounds them (smaller.pathological.ca/Flickr)

There’s something different about newborns’ blood. In babies less than 28 days of age, the immune system still hibernates—making newborns more susceptible to life-threatening infections and less responsive to many vaccines. Ofer Levy, MD, PhD, and his colleagues at Boston Children’s Hospital have done extensive work toward understanding the newborn immune system, and now they’ve uncovered a mechanism to help explain why the system is so weak—and how it might be strengthened.

“If we can understand the molecular mechanisms causing the immune system to be different when we’re very young or very old, we can leverage that knowledge to develop new treatments,” says Levy.

A vaccine that works in newborns?

If we could immunize infants at birth, far more could be protected from infections. (Photo: DFID-UK Dept for International Development)

Right now, immunizations against most infections begin at 2 months of age. But that leaves newborns at risk for infections like rotavirus, whooping cough and pneumococcus during a highly vulnerable time.

In resource-poor countries, this is a serious problem: Many children see a health care provider only at birth, so may miss their chance to be protected. Worldwide, each year, more than 2 million infants under 6 months old die from infections, especially pneumonia. If we could immunize infants at birth, it would be a huge win for global health.

Unfortunately, though, newborns don’t respond to most vaccines. Their immune systems are too immature—which is why few vaccines for newborns exist.

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First reported cure of a baby infected with HIV

HIV (green dots) budding from a white blood cell. (CDC)

AIDS and HIV have been with us for more than 30 years. In that time, millions have died and millions more have been able to keep the virus at bay with a cocktail of medications called highly active antiretroviral therapy, or HAART.

But of those millions, only one person has reportedly been cured. As of this week, that number may now be two.

A team of researchers at Johns Hopkins University Medical School reported at last weekend’s Conference on Retroviruses and Opportunistic Infections the case of a child believed to be born HIV-positive and who, by all available tests, is no longer carrying active virus in the blood.

The key, according to their report, was aggressive and near immediate HAART treatment, starting before the child was 30 hours old and continuing until she was a year and a half old.

“This finding is hopeful but requires further study,” says Sandra Burchett, MD, MSc, clinical director of our Division of Infectious Diseases and director of the Children’s Hospital AIDS Program. “We all agree that treating babies infected with HIV as soon as possible maintains a healthy immune system; what we do not know is when, if ever, it is safe to stop HAART. Treating adults early after infection is not curative, but it may be that babies are somehow different.

“It is critically important, though,” she cautions, “for children, youth and young adults with HIV who are on HAART now to keep taking their medications, not stop on their own to see if they too are cured.”

Some question, though, whether the child was ever actually infected. Her doctors started therapy so early because her mother had uncontrolled HIV, putting the child at extremely high risk of developing the infection herself.

The only other patient reportedly ever cured of HIV is a man named Timothy Ray Brown. In 2006, Brown received a bone marrow transplant for leukemia, but with a twist: the marrow donor had been chosen for harboring a rare genetic mutation that conferred resistance to HIV. According to a paper published in the New England Journal of Medicine in 2009, Brown has been off HAART treatment since 2007 with little to no sign of infection.

Want to learn more? Click here to read an online Q&A with Burchett hosted by The Guardian on March 5.

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Modeling sepsis in newborns: toward better detection and treatment

Sepsis, a serious, hard-to-diagnose threat in the NICU, can interfere with a baby’s development even when cleared with antibiotics. (Image: Army Medicine/Flickr)

Sepsis, or bacterial infection of the bloodstream, is a grave threat to premature infants in the neonatal intensive care unit (NICU) who have catheters and intravenous lines. Even when antibiotics clear the infection itself, the inflammation that it causes can do just as much damage. Not only can sepsis and the resulting inflammation interfere with fragile preemies’ ability to gain weight, but a growing literature suggests that they can impair brain development.

Preventive measures can now avoid many cases of sepsis, but those that slip through can be hard to detect in newborns.

“Newborns can’t speak, and they have unique immune systems, so they tend not to have fevers or show clinical signs,” explains Ofer Levy, MD, PhD, of the Division of Infectious Diseases at Boston Children’s Hospital. “There may be irregular breathing or increased heart rate, or the baby may be acting a little ‘off,’ but these signs are pretty nonspecific. There’s a tremendous need for better diagnostics in this field.”

Levy and colleagues recently described a mouse model that, for the first time, captures the effects of sepsis on the newborn immune system. They and others have begun using it to identify diagnostic markers and better treatments.

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A distant star: a single vaccine at birth

Ofer Levy is nothing if not passionate. Talking about his new project, he starts taking notes on my pad for me, to make sure I catch every detail. When Levy was getting his MD/PhD at NYU, one of his mentors told him, “In pursuing your life’s passion as a researcher, you should set your sights on a distant star.”

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