Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

Trivedi, Shubhanshi; Labuz, Daniel; Anderson, Cole P; Araujo, Claudia V; Blair, Antoinette; Middleton, Elizabeth A; Jensen, Owen; Tran, Alexander; Mulvey, Matthew A; Campbell, Robert A; Hale, J Scott; Rondina, Matthew T; Leung, Daniel T

Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients at sepsis presentation were significantly reduced in frequency compared to healthy donors, and were more activated, with decreased IFN-γ production, compared to both healthy donors and paired 90-day samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.