Phenotypic changes of mucosal-associated invariant T (MAIT) cells during and after acute human sepsis

Abstract

Abstract Sepsis is a devastating syndrome that is characterized by organ dysfunction caused by a hyperinflammatory environment following a dysregulated immune response to an infection. Aside from the initial insult of sepsis, patients who survive are at risk of immunosuppression, likely due to the impact of sepsis on both innate and adaptive immunity. There remains a lack of effective interventions for sepsis, possibly due to incomplete understanding of its pathobiology. MAIT cells are innate-like T cells that possess features of both innate and adaptive immunity and are activated by microbial-derived compounds of the riboflavin synthesis pathway, restricted by the evolutionarily conserved receptor MHC class-1 related protein (MR1). We aim to study the role that MAIT cells play during and after acute sepsis. We obtained blood and isolated peripheral blood mononuclear cells from 12 paired septic patients during acute sepsis and 90 days after diagnosis of sepsis, and age and sex-matched healthy donor controls. Using flow cytometry, we see that acute septic patients’ MAIT cells are highly activated and show higher inhibitory receptor expression compared to healthy donors and convalescent patients’ MAIT cells. We show that acute septic patient’s MAIT cells produced significantly less interferon gamma, and lower IFNG expression compared to paired convalescent patients after ex vivo stimulation with E. coli. Further investigation into other effectors of MAIT cells is ongoing. Our data suggest that acute septic patients’ MAIT cells are highly activated and are dysfunctional upon stimulation with E. coli. The understanding of the biological role of MAIT cells during and after acute sepsis can provide a novel therapeutic strategy for septic patients.