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

Elife. 2020 Nov 9;9:e55615. doi: 10.7554/eLife.55615.

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.

Keywords: MAIT cells; human; immunology; inflammation; innate-like T cell; medicine; mouse; sepsis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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