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Newborns' weak immunity has upside: immune suppression in infants lets beneficial microbes in.

The seeming failure of newborns to muster a robust defense against infections is a trade-off that delivers long-term benefits, a new study suggests. In infants, the body's immune army stands down for a month or two and then gears up. This gap may allow beneficial bacteria to populate an infant's intestines, researchers working with mice report November 6 in Nature.

Neonates' lackluster immunity may be "a normal developmental feature," says biochemist Sidney Morris Jr. of the University of Pittsburgh School of Medicine, who wasn't involved in the study.

The human body houses billions of helpful microbes, called commensal bacteria, which digest nutrients and provide other services, says study coauthor Sing Sing Way, an infectious disease pediatrician at Cincinnati Children's Hospital Medical Center. "They occupy a niche that prevents more-pathogenic bacteria from occupying the intestines," he says.

In newborn humans and mice, these microbes need to get ensconced in the intestines without the immune system spotting them and calling in the troops.

Way's team found that an immature form of red blood cell is instrumental in toning down immune reactions against microbes in neonatal mice. These still-developing cells, which have a protein on their surface called CD71, also show up in abundance in the umbilical cord blood of human babies, the team showed. In mice, the cells appear to orchestrate immune suppression by making an enzyme called arginase-2, which in turn sends "stop" signals to inflammatory immune cells.

In a series of experiments, the scientists found many more CD71 cells in 6-day-old neonatal mice than in adult mice, resulting in lower levels of inflammatory proteins in the neonates. That left the young mice hospitable to newly arriving microbes. When the scientists depleted the animals' CD71 cells, a vigorous immune defense ensued against the microbes.

Immune tolerance toward microbes wore off in the mice over three weeks--a period that corresponds to one to two months in humans, Way estimates. At 21 days, the mice's CD71 cell numbers equaled those of 8-week-old adult mice, contributing little to immune suppression.

"This is great. It's a beautiful piece of work," says Mike McCune, an infectious disease physician at the University of California, San Francisco. Doctors might someday be able to adjust immune suppression in newborns as needed to welcome more commensal bacteria or fend off pathogens that pose risks.

Newborn immunity involves more than just CD71 cells; breast milk plays a big role by delivering protective antibodies as it tones down the baby's own defenses. But in general, the new immune suppression findings suggest an evolutionary trade-off with big returns. Infections are common in newborns, Way says, "and maybe 1 or 2 percent of newborns get seriously infected. But 100 percent need to be colonized with commensal bacteria."

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Title Annotation:BODY & BRAIN
Author:Seppa, Nathan
Publication:Science News
Date:Dec 14, 2013
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