Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection

PLoS One. 2019 Sep 27;14(9):e0223025. doi: 10.1371/journal.pone.0223025. eCollection 2019.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Cefoperazone / administration & dosage
  • Cefoperazone / adverse effects
  • Clostridium Infections / etiology
  • Clostridium Infections / immunology*
  • Clostridium Infections / microbiology
  • Clostridium Infections / therapy
  • Disease Models, Animal
  • Disease Resistance / genetics*
  • Disease Resistance / immunology
  • Fecal Microbiota Transplantation
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Knockout
  • Minor Histocompatibility Antigens / genetics*
  • Minor Histocompatibility Antigens / immunology
  • Mucosal-Associated Invariant T Cells / immunology
  • Specific Pathogen-Free Organisms

Substances

  • Anti-Bacterial Agents
  • Histocompatibility Antigens Class I
  • Minor Histocompatibility Antigens
  • Mr1 protein, mouse
  • Cefoperazone

Grants and funding

This work was also supported by an Inter-Agency Agreement to PC between the National Institutes for Health and Food and Drug administration (AAI17016-001-00001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.