Goblet cell-associated antigen passages are reduced during enteric infection (MUC4P.831)

Abstract

Abstract The intestinal mucosa is continually exposed to foreign antigens derived from the diet, commensal bacteria, and pathogens. Regulating the exposure of the immune system to this broad array of antigens is crucial to ensure intestinal homeostasis and to respond appropriately to enteric infections. Using in vivo two-photon imaging of the intestine of live mice, we recently demonstrated that under steady state conditions a subset of small intestinal goblet cells (GCs) transport luminal antigens to CD103+ dendritic cells (DCs) by forming goblet cell-associated antigen passages (GAPs). To understand how enteric infection altered GCs and GAPs, we infected mice with wildtype fluorescently labeled Salmonella typhimurium and evaluated GCs and GAPs using fluorescence microscopy. Within hours of intraluminal exposure, Salmonella preferentially localized around and within GCs that had formed GAPs. 24 hours after oral Salmonella infection, a subset of GCs were found to be apoptotic, and 72 hours after infection, GAPs were significantly decreased beyond the level of GC apoptosis. Salmonella infection resulted in epithelial activation of the epidermal growth factor receptor (EGFR), a potential regulator of GC secretion and GAP formation. These observations indicate that GAPs may provide a portal of entry for pathogens, and that GAP formation is reduced following enteric infection potentially to avoid delivery of luminal antigen to lamina propria immune cells in a hostile environment.