MAIT cell surveillance of a microbial metabolic pathway induced upon colitis

Changes in the composition and metabolic activity of the microbiota underlie many pathological processes, but how the host monitors such changes remains poorly understood. Mucosal associated invariant T (MAIT) cells recognize metabolites from the microbial riboflavin pathway presented by the MHC-related molecule MR1. Riboflavin contributes to bacterial respiration and oxidative stress resistance, but why T cells recognize riboflavin adducts is unclear. Here we show that hypoxia disruption in the colon, upon antibiotic treatment or intestinal inflammation, drives MAIT antigen production by the microbiota and triggers a protective MAIT cell response. The gene ribD, which controls MAIT antigen production, was over-expressed by Bacteroidaceae, Clostridiaceae and Enterobacteriacea during colitis. Riboflavin production provided a fitness advantage to Escherichia coli in the inflamed intestine. Riboflavin adducts crossed the intestinal barrier and induced T cell receptor (TCR) signalling in MAIT cells, which produced the tissue-repair mediator amphiregulin and reduced colitis severity. Thus, MAIT cells directly monitor a bacterial metabolism associated with intestinal inflammation and provide host protection in return. The study helps understand the role of T cell recognition of riboflavin metabolites. The new host-microbiota interaction described could explain MAIT cell activation in other pathologies associated with dysanaerobiosis such as obesity and colorectal cancer.