Oral Presentation International Veterinary Immunology Symposium 2016

Host-pathogen interactions at the intestinal epithelium regulate barrier integrity and immunity to bacterial enteropathogens via IL17 (#72)

Yu Luo 1 , Eric Cox 1 , Bert Devriendt 1
  1. Ghent university, Merelbeke, OOST-VLAANDEREN, Belgium

Enteric diseases remain a global health issue and despite many efforts, no subunit vaccines are currently available to prevent infections with enteropathogens. A significant hurdle to successful vaccine design is the poor understanding of host-pathogen interactions and how these affect intestinal immunity. A myriad of foreign antigens derived from food, microbiota and pathogens daily flood the gastro-intestinal immune system. To prevent these potentially hazardous molecules from gaining access to the host, a single layer of epithelial cells, mostly enterocytes, lines the intestinal tissues. These enterocytes not only function as a barrier to keep these macromolecules at bay, they also inform underlying immune cells on the gut luminal content and as such create and sustain a tolerogenic environment during steady state conditions. During infection however enterocytes recognize pathogens and relay this information to induce an immunogenic environment, enabling antigen-presenting cells (APCs) to mount adequate pathogen-specific immunity. This crosstalk between the intestinal epithelium and APCs plays a key role in shaping the local micro-environment towards tolerance or immunity. In case of bacterial enteropathogens, it ultimately results in the secretion of IL17A by innate immune cells and Th17 cells to promote secretory IgA responses. Our results now add a third player to this game, as intestinal epithelial cells also produce IL17A upon sensing enteropathogens. Indeed, in pigs infected a with enterotoxigenic E. coli (ETEC), a major cause of postweaning diarrhea in piglets, not only an intestinal Th17 cell response was observed, but ETEC-derived enterotoxins also triggered intestinal epithelial cells to produce IL17A, which further regulated the transcription of genes (antimicrobial peptides, mucins, …) involved in maintaining the integrity of the epithelial barrier. These findings unravel a novel role for epithelial-derived IL-17A in intestinal immunity to enteropathogens and may inform on the design of prophylactics fortifying the intestinal epithelial barrier to prevent enteric diseases.