Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection

Posted by: | October 15, 2019 | Comments


Experimental design for experiments performed in this study

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.

Read more at: PLoS ONE

Smith AD, Foss ED, Zhang I, Hastie JL, Giordano NP, Gasparyan L, et al. PLoS ONE. DOI: https://doi.org/10.1371/journal.pone.0223025. 27 Sep 2019.

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