Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis
Shubhanshi Trivedi, Daniel Labuz, Cole Anderson, Claudia V. de Araujo, Antoinette Blair, Elizabeth A. Middleton, Owen Jensen, Alexander Tran, Matthew A. Mulvey, Robert A. Campbell, J. Scott Hale, Matthew T. Rondina, Daniel T. Leung
Abstract
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.