Mucosal-associated invariant T (MAIT) cells are reduced and dysfunctional in acute melioidosis

Abstract

Abstract Burkholderia pseudomallei (BP), the causative agent of melioidosis, is a major cause of sepsis in Southeast Asia, especially in people with diabetes mellitus (DM). The role of Mucosal-associated invariant T (MAIT) cells; innate-like T cells important for antibacterial immunity; in melioidosis is unknown. We measured MAIT cell activation by BP in vitro using co-culture assays with THP-1 cells, and evaluated MAIT cell frequency, activation, and function ex vivo in an observational cohort (n = 120) of melioidosis patients and endemic controls with and without DM in Thailand. We show that BP induces IFN-γ secretion by MAIT cells in a cytokine dependent manner. In acute melioidosis, circulating MAIT cells, particularly the double-negative (DN) subset, were significantly reduced, and highly activated but dysfunctional, with reduced IFN-γ responses to BP and E. coli which were restored upon recovery. Among acute patients, non-survivors showed lower granzyme B and IFN-γ expression. Acute melioidosis patients with DM co-morbidity exhibited reduced DN MAIT cell frequency and responses to E. coli compared to non-DM patients. Overall, the frequency and function of MAIT cells is impaired during acute melioidosis, especially in patients with DM, indicating a key role for these cells in antibacterial defence and disease susceptibility.