Does host immunity contribute to susceptibility to infection? The role of MAIT cells in Clostridium difficile Infection.

Susceptibility to Clostridium difficile (Cd) infection (CDI) occurs following disruption of the gut microbiome1. Mucosa-associated invariant T (MAIT) cells are a specialized population of innate T cells. MAIT cells recognize intermediates of riboflavin biosynthesis, a pathway found only in microbes, making MAIT development dependent on the host microbiome. While MAIT cells are important in combatting pulmonary infections, their role in CDI remains undetermined2. Since MAIT cells are found in relatively high numbers in the gut, we hypothesized that they would be critical in controlling Cd colonization3. WT and MR1-/- (lacking MAIT cells) mice were given antibiotics and infected with Cd spores. Astonishingly, MR-/- mice were resistant to Cd colonization. To determine the role of the microbiome in this resistant phenotype, mice were given fecal microbiota transplant (FMT) prior to infection and fecal samples were sequenced. WT mice given FMT from MR1-/- mice showed decreased colonization by day 7 and clearance of Cd by day 14, while the WT mice given control FMT remained colonized at high levels (109) throughout. These data suggest the microbiome associated with MR-/- mice leads to colonization resistance and differences in the microbiota composition of these two mouse strains is currently under investigation.