Exposure to microbial antigens during early life is required for the establishment of tolerance to commensal <a>bacteria</a>

Abstract

Abstract Current pediatric guidelines recommend breastfeeding and avoidance of oral antibiotics in the first years of life to reduce the risk of development of allergies. Additionally, animal models have shown exposure to the microbiota prior to weaning is necessary for the prevention of asthma or inflammatory diseases later in life. These studies suggest exposure to commensal microbes prior to weaning supports the development of tolerogenic responses in the intestinal tract. This interval of life coincides with the development of regulatory T cells in the colon which can suppress inflammatory responses. We have recently described a critical window for the development of tolerance in mice and found exposure to microbial antigens between 10 and 21 days of life occurred via the colon and induced long lived antigen specific FoxP3+ regulatory T cell responses. This window of tolerance is defined and regulated by ligands found in breastmilk and in the microbial milieu, and exposure to the microbial antigens required goblet cell associated antigen passages. Regulatory T cells developing during early life were required to restrain inflammatory responses against commensals later in life in a model of colitis. Additionally, exposure to commensal antigens via the colon after day of life 21 resulted in robust antigen-specific T effector responses and exacerbated inflammation in a model of colitis, exhibiting the critical nature of regulating this window of tolerance. Thus, exposure to microbial antigens early in life is an imperative element to the development of tolerance, and is highly regulated to prevent inflammation against the commensal microbiota.