%0 Journal Article
%T Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18
%A Ana C. S. Palmer
%A Crystle Calvin
%A Guo Zhong
%A Kellyanne Duncan
%A Mayara Grizotte-Lake
%A Namrata Iyer
%A Nina Isoherranen
%A Sarah R. Gordon
%A Shipra Vaishnava
%J -
%D 2020
%R 10.1371/journal.ppat.1008360
%X Intestinal epithelial cells (IECs) are at the forefront of host-pathogen interactions, coordinating a cascade of immune responses to protect against pathogens. Here we show that IEC-intrinsic vitamin A signaling restricts pathogen invasion early in the infection and subsequently activates immune cells to promote pathogen clearance. Mice blocked for retinoic acid receptor (RAR) signaling selectively in IECs (stop¦¤IEC) showed higher Salmonella burden in colonic tissues early in the infection that associated with higher luminal and systemic loads of the pathogen at later stages. Higher pathogen burden in stop¦¤IEC mice correlated with attenuated mucosal interferon gamma (IFN¦Ã) production by underlying immune cells. We found that, at homeostasis, the intestinal epithelium of stop¦¤IEC mice produced significantly lower amounts of interleukin 18 (IL-18), a potent inducer of IFN¦Ã. Regulation of IL-18 by vitamin A was also observed in a dietary model of vitamin A supplementation. IL-18 reconstitution in stop¦¤IEC mice restored resistance to Salmonella by promoting epithelial cell shedding to eliminate infected cells and limit pathogen invasion early in infection. Further, IL-18 augmented IFN¦Ã production by underlying immune cells to restrict pathogen burden and systemic spread. Our work uncovers a critical role for vitamin A in coordinating a biphasic immune response to Salmonella infection by regulating IL-18 production by IECs
%K Salmonellosis
%K Vitamin A
%K Colon
%K Retinoic acid signaling cascade
%K Retinoid signaling
%K Epithelial cells
%K Salmonella
%K Mouse models
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008360