Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18

• DOI: 10.1371/journal.ppat.1008360
• Publication Date: 2020-04-24T17:39:03Z
• Authors: Namrata Iyer; Mayara Grizotte-Lake; Kellyanne Duncan; Sarah R. Gordon; Ana C. S. Palmer; Crystle Calvin; Guo Zhong; Nina Isoherranen; Shipra Vaishnava
• Keywords: Intestinal epithelium

Intestinal epithelial cells (IECs) are at the forefront of host-pathogen interactions, coordinating a cascade immune responses to protect against pathogens. Here we show that IEC-intrinsic vitamin A signaling restricts pathogen invasion early in infection and subsequently activates promote clearance. Mice blocked for retinoic acid receptor (RAR) selectively IECs (stopΔIEC) showed higher Salmonella burden colonic tissues associated with luminal systemic loads later stages. Higher stopΔIEC mice correlated attenuated mucosal interferon gamma (IFNγ) production by underlying cells. We found that, homeostasis, intestinal epithelium produced significantly lower amounts interleukin 18 (IL-18), potent inducer IFNγ. Regulation IL-18 was also observed dietary model supplementation. reconstitution restored resistance promoting cell shedding eliminate infected limit infection. Further, augmented IFNγ restrict spread. Our work uncovers critical role biphasic response regulating IECs.