MAIT cells: Shaping the microbiome, contributing to Clostridium difficile infection

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.216-216.3
• Main Authors: Smith, Ashley Dawn, Zhang, Irma T, Schubert, Alyxandria M, Giordano, Nicole P, Hastie, Jessica E, Cowley, Siobhan C, Carlson, Paul E
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.216.3

Clostridium difficile (Cd) is a leading cause of nosocomial infection. Cd infection (CDI) typically occurs following antibiotic usage, which perturbs the gut microbiota leaving the host susceptible to Cd colonization. Mucosa-associated invariant T cells (MAIT) cells recognize intermediates of riboflavin biosynthesis presented on MR1, an MHC-I like related molecule. MAIT cell development is dependent on the host microbiome. MAIT cells are found in high numbers at mucosal sites and are beneficial in combatting various pulmonary infections; however their role in gut infections is unknown. We hypothesized that MAIT cells would play a role in controlling CDI. To test this hypothesis, WT and MR1−/−(lacking MAIT cells) mice were treated with antibiotics and then infected with Cd spores. Stool was collected and plated to determine Cd colonization levels for several days post-infection. Contrary to our hypothesis, MR1−/− mice showed no signs of disease or detectable levels of Cd colonization. More pathogenic strains of Cd were also tested and MR1−/− mice remained resistant. Fecal microbiota transplantation (FMT) was conducted to determine the role of the microbiota in this resistance phenotype. Susceptible WT mice given FMT from MR1−/− mice experienced dramatically lower colonization levels by day 7 and cleared detectable Cd by day 14, while WT mice given control FMT continued to exhibit high colonization levels. 16S rRNA sequencing of fecal samples from each strain revealed inherent phylum level differences in relative abundance of Bacteroidetes, Firmicutes, and Verrucomicrobia after antibiotics and FMT. Our data suggest the MR1−/− gut microbiome is resistant to Cd colonization, and this resistance is transferrable via FMT.