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Sci Immunol. 2017 Dec 15;2(18). pii: eaao1314. doi: 10.1126/sciimmunol.aao1314.

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

Author information

1
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
3
Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
4
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. rnewberry@wustl.edu.

Abstract

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.

PMID:
29246946
PMCID:
PMC5759965
DOI:
10.1126/sciimmunol.aao1314
[Indexed for MEDLINE]
Free PMC Article

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