Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria

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Science Immunology  15 Dec 2017:
Vol. 2, Issue 18, eaao1314
DOI: 10.1126/sciimmunol.aao1314

Licensing microbes for symbiosis

Gut microbiota have several important functions, including aiding host metabolism and limiting pathogen invasion by competing for essential nutrients. To establish and sustain this symbiotic relationship, it is vital that the host develops tolerance to gut microbial antigens early in life. Here, Knoop et al. demonstrate in mice that tolerance to symbionts in the gut develops between 10 and 20 days after birth, and is perfectly synchronized with the formation of goblet cell–associated antigen passages (GAPs) in the colon, which facilitate transport of bacterial antigens from the lumen to the lamina propria. Their findings suggest that the development of this particular type of microbial tolerance is restricted to microbes that colonize the colon early in life.


We have a mutually beneficial relationship with the trillions of microorganisms inhabiting our gastrointestinal tract. However, maintaining this relationship requires recognizing these organisms as affable and restraining inflammatory responses to these organisms when encountered in hostile settings. How and when the immune system develops tolerance to our gut microbial members is not well understood. We identify a specific preweaning interval in which gut microbial antigens are encountered by the immune system to induce antigen-specific tolerance to gut bacteria. For some bacterial taxa, physiologic encounters with the immune system are restricted to this interval, despite abundance of these taxa in the gut lumen at later times outside this interval. Antigen-specific tolerance to gut bacteria induced during this preweaning interval is stable and maintained even if these taxa are encountered later in life in an inflammatory setting. However, inhibiting microbial antigen encounter during this interval or extending these encounters beyond the normal interval results in a failure to induce tolerance and robust antigen-specific effector responses to gut bacteria upon reencounter in an inflammatory setting. Thus, we have identified a defined preweaning interval critical for developing tolerance to gut bacteria and maintaining the mutually beneficial relationship with our gut microbiota.

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