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

Autor: Iyer N; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States of America., Grizotte-Lake M; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States of America., Duncan K; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States of America., Gordon SR; Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, United States of America., Palmer ACS; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States of America., Calvin C; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States of America., Zhong G; Department of Pharmaceutics, University of Washington, Seattle, WA, United States of America., Isoherranen N; Department of Pharmaceutics, University of Washington, Seattle, WA, United States of America., Vaishnava S; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Apr 24; Vol. 16 (4), pp. e1008360. Date of Electronic Publication: 2020 Apr 24 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008360
Abstrakt: 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 (stopΔIEC) 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 stopΔIEC mice correlated with attenuated mucosal interferon gamma (IFNγ) production by underlying immune cells. We found that, at homeostasis, the intestinal epithelium of stopΔIEC mice produced significantly lower amounts of interleukin 18 (IL-18), a potent inducer of IFNγ. Regulation of IL-18 by vitamin A was also observed in a dietary model of vitamin A supplementation. IL-18 reconstitution in stopΔIEC 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 IFNγ 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje