Mucosal-associated invariant T (MAIT) cell responses in Salmonella enterica serovar Typhi strain Ty21a oral vaccine recipients

Abstract

AbstractBackgroundMucosal–associated invariant T (MAIT) cells are unconventional innate-like T cells abundant in mucosal tissue of humans, and associated with protective responses to microbial infections. MAIT cells have capacity for rapid effector function, including the secretion of cytokines and cytotoxic molecules. However, limited information is available regarding the activity of MAIT cells in mucosal vaccine-mediated immune responses in humans.MethodsWe enrolled healthy adults who received a course of oral live-attenuated S. Typhi strain Ty21a vaccine and collected peripheral blood samples pre-vaccination, and at 7 days and one month post-vaccination. We used flow cytometry, cell migration assays, and tetramer decay assay to assess MAIT cell responses.ResultsWe show that following vaccination, circulating MAIT cells are decreased in frequency but have increased activation markers. Post-vaccine timepoints had higher levels of MAIT cells expressing gut-homing marker integrin α4β7 and chemokine receptor CCR9, suggesting the potential of MAIT cells to migrate to mucosal sites. While we found higher frequencies of TNF-α expression on MAIT cells post-vaccination, we did not find significant differences in expression of other effector molecules, TCR avidity, or cell migration.ConclusionsWe show how MAIT cell immune responses are modulated post-vaccination against S.Typhi. This study contributes to our understanding of MAIT cells’ potential role in oral vaccination against bacterial mucosal pathogens.