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 presenting with sepsis were significantly reduced in frequency, more activated, and had decreased IFN-γ production when stimulated, compared to healthy donors and paired 90-day post-sepsis 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.

Longitudinal analysis of mucosa‐associated invariant T cells in sepsis reveals their early numerical decline with prognostic implications and a progressive loss of antimicrobial functions

“…Therefore, in their steady state, MAIT cells alone are neither protective nor pathogenic in the context of acute sepsis. This is inconsistent with the findings of Trivedi et al 34 who reported increased bacteremia and mortality in Mr1 À/À mice following CLP. These investigators compared Mr1 À/À and Mr1 +/+ C57BL/6 mice in their study.…”

Mucosal-Associated Invariant T Cells as a Possible Target to Suppress Secondary Infections at COVID-19

“…We hypothesize that secondary non-viral infections may enhance the severity of COVID-19 by activating MR1-dependent MAIT cells. MAIT cells promote protection against primary infections through cytokines production (24), as well as mediate protective host responses in sepsis by reducing bacterial burden (25). However, in the case of secondary infections, additive inflammation can exacerbate the situation due to the progression of the cytokine storm.…”

Balanced Input from the tRNA Prenyltransferase MiaA Controls the Stress Resistance and Virulence Potential of Extraintestinal PathogenicEscherichia coli

“…Following i.p. injection, the bacteria enter the bloodstream and disseminate [56,64,65]. In our experiments, only 15% (2/13) of the mice infected with wild-type UTI89, and 0% (0/13) of the mice injected with UTI89∆miaB, were viable after 48 hours (Fig.…”