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Mucosal associated invariant T MAIT cells are an evolutionary conserved T cell subset which recognize riboflavin precursor derivatives presented by MR1 Intestinal bacteria from the Bacteroidetes and Proteobacteria phyla can produce MAIT antigens suggesting a direct interplay between MAIT cells and the microbiota In humans MAIT cells have been implicated in pathologies associated with intestinal dysbiosis such as inflammatory bowel diseases but the role of MAIT cells in these diseases remains unknown Increased levels of oxygen and oxidative stress are hallmarks of intestinal inflammation and riboflavin contributes to bacterial respiration and to oxidative stress resistance suggesting increased needs for riboflavin during intestinal inflammation Supporting this hypothesis bacteria possessing the riboflavin biosynthesis pathway are enriched in Crohn s disease patients In the first part of this work we explored the hypothesis that MAIT cells monitor a bacterial metabolic pathway associated with altered gut ecosystem We showed that hypoxia disruption in the colon upon antibiotic treatment or dextran sodium sulfate DSS -induced colitis increased MAIT antigen production by the microbiota We sequenced the 16S rRNA genes from the cecum of antibiotic- and DSS-treated mice and analyzed expression of the riboflavin pathway genes in the Helicobacter hepaticus model of colitis Dysanaerobiosis was associated with expansion of Enterobacteriaceae upon vancomycin treatment and Bacteroidaceae and Enterobacteriaceae in colitic mice Riboflavin production provided a fitness advantage to Escherichia coli in the inflamed intestine Both Bacteroidaceae and Enterobacteriaceae can produce high amounts of MAIT antigens in vitro In the H hepaticus model of colitis ribD which controls MAIT antigen production was over-expressed by Bacteroidaceae Clostridiaceae and Enterobacteriaceae during colitis MAIT antigens 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 In the second part of this work we characterized MAIT cells in the ileal environment wherein high levels of oxygen have been observed at steady state A range of bacteria that encode the riboflavin pathway populated the ileum however ileal MAIT cells were not activated through TCR engagement and expressed distinct phenotypic profiles We discuss the future studies that will be needed to understand MAIT-microbiota interactions in the ileum Collectively in the colon MAIT cells directly sense and react to changes in bacterial metabolism associated with intestinal inflammation and provide host protection in return This new host-microbiota interaction may explain MAIT cell activation in other pathologies associated with dysbiosis such as colorectal cancer

Les cellules MAIT et la riboflavine dans les interactions hôte-microbiote

L'immunité innée dans le diabète sucré

Publication search with Mait as keyword

Les cellules MAIT et la riboflavine dans les interactions hôte-microbiote

L'immunité innée dans le diabète sucré

Publication search
with Mait as keyword