Luminal microbial sensing regulates colonic goblet cell associated antigen passages through the activation of p42/p44 MAPK and the EGFR (P3154)

Abstract

Abstract The intestinal tract is full of proteins ranging in antigenicity from inert food antigens to potential pathogens and bacterial toxins. A major focus of mucosal immunology is to better understand how these antigens are acquired and introduced to the immune system. Using intravital two-photon imaging we recently showed that in conventionally housed mice, small intestinal goblet cells, but not colonic goblet cells, act as a route of antigen delivery to intestinal dendritic cells by forming goblet cell-associated antigen passages (GAPs), in a mechanism linked to goblet cell secretion. In contrast to conventionally housed mice, we observed that GAPs were present in the colon of germfree mice, mice given antibiotics, and, surprisingly, neonatal mice. We found that the activation of p44/p42 MAPK and EGFR in colonic goblet cells correlated with the presence of luminal microbiota and the ability to sense the flora via TLRs. Inhibition of either p42/p44 MAPK or EGFR allowed GAP formation to occur in the colon of SPF housed mice, and colonic GAPs in germfree mice were blocked by activation of the EGFR. These observations indicate that sensing the enteric flora inhibits colonic GAP formation. This regulation of antigen delivery would allow sampling of luminal antigens when the environment is permissive, such as in the homeostatic small intestine, but would prevent sampling luminal antigens in a hostile environment, such as the high microbial load in the colon or during infection.