Mucosal-Associated Invariant T (MAIT) Cells are Highly Activated in Duodenal Tissue of Humans with Vibrio cholerae O1 Infection

Abstract

AbstractMucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes with a semi-conserved TCRα, activated by the presentation of vitamin B metabolites by the MHC-I related protein, MR1, and with diverse innate and adaptive effector functions. The role of MAIT cells in acute intestinal infections, especially at the mucosal level, is not well known. Here, we analyzed the presence and phenotype of MAIT cells in duodenal biopsies and paired peripheral blood samples, in patients during and after culture-confirmed Vibrio cholerae O1 infection. Immunohistochemical staining of duodenal biopsies from cholera patients identified MAIT cells in the lamina propria, but not in the lining of villous and crypt epithelia. We observed significantly higher frequencies of duodenal MAIT cells at the acute stage (day 2) of V. cholerae infection as compared to late convalescence (day 30, p = 0.0049). By flow cytometry, we showed that duodenal MAIT cells are more activated than peripheral MAIT cells (p < 0.01 across time points), although there were no significant differences between duodenal MAITs at day 2 and day 30. We found fecal markers of intestinal permeability and inflammation to be correlated with the loss of duodenal (but not peripheral) MAIT cells, and single-cell sequencing revealed differing T cell receptor usage between the duodenal and peripheral blood MAIT cells. In summary, we show that MAIT cells are present and highly activated in the lamina propria of the duodenum during V. cholerae infection. Future work into the trafficking and tissue-resident function of MAIT cells is warranted.