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

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.

• Authors: Shubhanshi Trivedi, Daniel Labuz, Cole P Anderson, Claudia V 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
• Journal: eLife (Elife) Vol. 9 (11 09 2020) ISSN: 2050-084X [Electronic] England
• PMID: 33164745 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020, Trivedi et al.

Chemical References

• Biomarkers
• Cytokines
• Histocompatibility Antigens Class I
• Minor Histocompatibility Antigens
• Mr1 protein, mouse
• RNA, Messenger

Topics

• Animals
• Biomarkers
• Cytokines (genetics, metabolism)
• Female
• Histocompatibility Antigens Class I (genetics, metabolism)
• Humans
• Immunity, Innate
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Minor Histocompatibility Antigens (genetics, metabolism)
• Mucosal-Associated Invariant T Cells (physiology)
• RNA, Messenger (genetics, metabolism)
• Sepsis (immunology, metabolism)