One of newborns’ biggest vulnerabilities is largely invisible: In the weeks after birth, babies are especially susceptible to infection because their immune systems aren’t fully functional. There are a handful of theories to explain this liability, and now a research team has added a new one to the list: Immune suppression in early life might help prevent inflammation in the infants’ intestines as they become colonized by the helpful bacteria they need to stay healthy.Newborns are more likely than older babies to catch, and die from, serious infections. The reason is fuzzy—indeed, there may be more than one explanation. One theory is that much like their brains, their lungs, and the rest of their bodies, infants’ immune systems just haven’t fully matured yet. Another is that both mothers-to-be and their in utero companions have suppressed immune systems, so that neither rejects the other. After birth, the thinking goes, it takes babies a month or so to boost their immunity.Seeking new ways to better understand this process, Sing Sing Way, a pediatric infectious disease doctor at Cincinnati Children’s Hospital Medical Center in Ohio, wondered whether transferring immune cells from adults might rev up their immune systems. Yet when he and his colleagues injected infection-fighting cells from the spleens of adult mice into 6-day-old pups, nothing happened: The pups were just as vulnerable to harmful bacteria as control animals. Probing more deeply into this surprise, they found that the injected cells simply stopped functioning in the newborn animals. Then Way’s group did the reverse transplant—they gave adult mice newborn immune cells that were inactivated in the pups and found that they “turned on” in the mature animals. These experiments “told us it wasn’t a problem with the neonatal cells themselves,” Way says. 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Newborn mice, just like human babies, are born “clean,” with little intestinal bacteria. Very rapidly that changes. Way wondered whether there might be some connection between this colonization and what looked like a purposeful suppression of the immune system in his mice.To find out, his group focused on immune cells that eventually develop into red blood cells and that express a surface receptor called CD71, which causes immune suppression of other cells. Knocking out about 60% of these CD71 cells—as many as their technology could manage—was followed by significant inflammation in the intestines of the mouse pups. Way and his colleagues also found that, as the mice grew, fewer and fewer cells boasted CD71 receptors, suggesting the suppression wasn’t needed. He theorizes that that’s because the gut has been colonized by that point.The work, reported online today in Nature, “adds a new and very important chapter” to the story of how the immune system develops, says Mike McCune, an immunologist at the University of California, San Francisco. Immune suppression, at least in newborn mice, appears to reflect a purposeful shift in the balance of immune cells. The concept is definitely a plausible one, agrees Heather Jaspan, a pediatric infectious disease specialist and immunologist at the University of Cape Town and at Seattle BioMed in Washington. She wonders about other cell types, in addition to those with CD71 receptors, that might play a role. “It would be interesting to follow this up with more cause and effect studies,” she says, to nail down definitively that specific immune suppression allows bacteria to colonize the gut without harming a newborn.One big caveat is whether what Way’s team observed will hold up in human babies. A baby’s immune system develops differently than that of a mouse, and Way is interested in looking for CD71 cells in babies born around their due date, as well as those born prematurely. Very premature infants often die of a condition called necrotizing enterocolitis, a massive inflammation of the intestines. Way and McCune wonder if that’s driven partly by a lack of CD71 cells in these babies—if, essentially, their immune systems are still fetal, not ready for the natural colonization of gut bacteria that happens after they’re born. In theory—and far in the future—say the researchers, preemies could receive immune cells that would make their immune system more like a full-term baby’s, allowing their guts to stay healthy.