Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.

ABSTRACT: Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis. Infection in macrophage-specific aryl hydrocarbon receptor (AhR) knockout mice revealed that AhR activation induced transcriptional reprogramming in macrophages and increased bacterial clearance and host survival. However, culture supernatants from multiple bacterial pa

SUBMITTER: Keskey RC 

PROVIDER: S-EPMC11905502 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature