Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.
Major histocompatibility complex-related protein 1 (MR1) is a highly conserved receptor that presents non-peptide antigens to specialized subsets of T-cells including mucosa-associated invariant T (MAIT) cells and other less characterized MR1-restricted T cells. The specific metabolites presented by MR1 are derived from the riboflavin biosynthesis pathway, which mammals cannot produce; however, these metabolites are synthesized by many bacteria and fungi. MAIT cells are dependent on MR1 and the host microbiota for their development and peripheral expansion; therefore, germ-free mice lack detectable MAIT cells. In addition, MAIT cells are present in high proportions at mucosal sites, and differ from conventional T-cells in both function and antigen recognition. Specifically, MAIT cells function as innate-like T-cells and can respond quickly by producing pro-inflammatory cytokines and secreting perforin/granzyme for direct cytotoxic effect.
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