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

• DOI: 10.7554/elife.55615
• Publication Date: 2020-11-09T13:00:52Z
• Authors: Shubhanshi Trivedi; Daniel Labuz; Cole P Anderson; Claudia V Araujo; Antoinette Blair; Elizabeth A Middl...; Owen Jensen; Alexander Tran; Matthew A Mulvey; Robert A Campbell; J Scott Hale; Matthew T Rondina; Daniel T Leung
• Keywords: Male; QH301-705.5; Science; MAIT cells; Mucosal-Associated Invariant T Cells; sepsis; Minor Histocompatibility Antigens; Mice; Immunology and Inflammation; Sepsis; Animals; Humans; RNA, Messenger; Biology (General); Mice, Knockout; Q; Histocompatibility Antigens Class I; R; Middle Aged; Immunity, Innate; 3. Good health; Mice, Inbred C57BL; Medicine; Cytokines; innate-like T cell; Female; Biomarkers

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.