Research on Mouse Infection with Salmonella Typhimurium
The chromosome 19 open reading frame 18 (C19orf18) is a protein-coding gene. Based on our preliminary findings, C19orf18 is an interferon-inducible gene that is selectively upregulated in the intestine of mice during Salmonella Typhimurium (S.Tm) infection, however, its biological significance and functional role in the course of infection remain unclear. Here, we identify C19orf18 as a key regulator of S.Tm pathogenesis. Consistent results from both in vivo and in vitro experiments demonstrate that loss of C19orf18 markedly attenuates S.Tm-induced intestinal inflammation and promotes mucosal injury repair. Mechanistically, C19orf18 deficiency reshapes the infection-associated gut ecosystem by promoting the expansion of Verrucomicrobiota, particularly the beneficial genus Akkermansia, and drives amino acid metabolic reprogramming with a pronounced increase in tryptophan metabolism. The resulting tryptophan-derived metabolites contribute to epithelial restitution and suppression of inflammatory responses. Collectively, our study uncovers a previously unrecognized mechanism by which C19orf18 modulates host responses to a foodborne enteric pathogen and establishes a causal link between C19orf18-driven microbiota remodeling, metabolic reprogramming, and intestinal inflammatory outcomes.