Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection

Ashley D Smith; Elissa D Foss; Irma Zhang; Jessica L Hastie; Nicole P Giordano; Lusine Gasparyan; Lam Phuc VinhNguyen; Alyxandria M Schubert; Deepika Prasad; Hannah L McMichael; Jinchun Sun; Richard D Beger; Vahan Simonyan; Siobhán C Cowley; Paul E Carlson Jr

doi:10.1371/journal.pone.0223025

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.

Authors

Ashley D Smith¹, Elissa D Foss¹, Irma Zhang¹, Jessica L Hastie¹, Nicole P Giordano¹, Lusine Gasparyan², Lam Phuc VinhNguyen², Alyxandria M Schubert¹, Deepika Prasad^{1

2}, Hannah L McMichael¹, Jinchun Sun³, Richard D Beger³, Vahan Simonyan², Siobhán C Cowley¹, Paul E Carlson Jr¹

Affiliations

¹ Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial Pathogens and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
² High-performance Integrated Personal Environment, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
³ Division of Systems Biology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas, United States of America.

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.