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Tolerance to harmless skin bacteria develops soon after birth

Research from the University of California San Francisco (UCSF) has found that the adaptive immune system’s tolerance to the commensal bacteria that make up the skin microbiome develops very shortly after birth, according to a paper published in Immunity (Nov. 17, 2015; 43(5):1011–1021).

“There’s an early developmental window during which you can be exposed to bacteria and they’re seen as friendly—the immune system incorporates them and says, ‘Yes this is good, this is ‘self,’ and it will not mount an immune response,,” study coauthor Dr. Michael Rosenblum, a dermatologist and immunologist at UCSF, said in a press release from UCSF (Nov. 17, 2015). “If you introduce the same bacteria for the first time later in life, the response is completely different. The immune system says, ‘This is bad, and we need to get rid of it.’”

Dr. Rosenblum and his colleagues introduced an antigen linked to the Epi-2W fluorescent protein into a strain of the common skin bacteria Staphylococcus epidermidis, so that they could track immune response to the tagged bacteria.

“Before this study, nobody had ever successfully modified a commensal skin microbe to enable an anti-commensal immune response to be precisely analysed,” Dr. Rosenblum said in the release. “Epi-2W should be a great research tool for understanding the skin microbiome, because ‘Staph epi’ is the quintessential human commensal skin microbe.”

When the test bacteria was introduced to the skin of naïve adult mice, there was an effector T-cell response but no overt inflammation, according to the findings. However, when those same mice had S. epidermidis introduced to minor abraisions, inflammation and activation of T cells against the bacteria was observed, showing the mice had not become immune tolerant to it.

When the experiment was repeated with week-old mice, the second exposure of the bacteria—to abrasions—produced very little inflammation and T cell activation.

When the authors investigated the response in baby mice closer, they found a parallel influx of regulatory T cells unique to the skin during the first two weeks of life. These regulatory T cells, which reduce the response of effector T cells, appears to be necessary for the development of tolerance to S. epidermidis, according to the paper.

“If we colonized the mice with Epi-2W bacteria in adulthood, it was almost like immunizing them—they mounted a strong immune response,” Dr. Rosenblum said. “But if we introduced the bacteria to the mice in the first 13 days of life they didn’t respond to it at all in adulthood. They were totally tolerant of the bacteria.”

Dr. Rosenblum said in the release that as it appears that bacteria must be present on the skin during an early developmental window if tolerance is to be developed, giving small infants antibiotics and removing certain species of bacteria may limit the species they are tolerant to later in life. That could in turn lead to chronic skin inflammation as the child ages.

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