Enteric antigens are delivered to the infant colonic immune system to promote enhance and long-lasting tolerance (MUC8P.801)

Abstract

Abstract Epidemiological studies indicate early exposure to microbial and dietary antigens via the gastrointestinal (GI) tract is associated with a decreased susceptibility for food allergy and inflammatory bowel disease later in life. However, the properties of the infant GI tract conferring this benefit are largely unknown. We found introduction of a dietary antigen during infancy, as opposed to early adulthood, promoted enhanced and lasting tolerance. Using in vivo imaging and ex vivo analysis of lamina propria antigen presenting cells following intraluminal antigen administration, we observed, in contrast to adults, enteric antigens were delivered to the colonic immune system in infants, which had an increased tolerogenic capacity. Antigen delivery to the infant colon immune system was mediated by goblet cell-associated antigen passages (GAPs) and the formation of colonic GAPs was regulated by goblet cell intrinsic sensing of the luminal microbiota, which inhibited antigen delivery and GAP formation in the colon as the microbiota expanded after weaning. Additionally, inhibition of colonic GAPs during enteric antigen exposure during infancy abrogated the tolerance induction. We propose antigen delivery to the infant colon allows the immune system to become ‘educated’ to dietary and microbial antigens, preventing responses to innocuous antigens encountered in the adult colon where the environment contains abundant and complex microbial stimuli.