Sci Rep. 2026 Jun 15.
Fazle Rabbi Chowdhury,
Martha Zewdie,
Priyanka Abraham,
Srija Moulik,
Hadiza Adebowale,
Jennifer Hill,
Md Robed Amin,
Lovely Barai,
Md Rokibul Hasan,
Ayako Kurioka,
Patpong Rongkard,
Direk Limmathurotsakul,
Nicholas P J Day,
Parinya Chamnan,
Paul Klenerman,
Chris B Willberg,
Barbara Kronsteiner,
Susanna J Dunachie.
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.
Keywords: Diabetes; Melioidosis; Mucosal associated invariant T cells; Sepsis