The MAIT cell response to controlled oral enterotoxigenic E. coli challenge

Mucosal-associated invariant T (MAIT) cells recognize conserved microbial antigens presented by the non-polymorphic MR1 molecules and play important roles in barrier immunity. Enterotoxigenic E. coli (ETEC) is a major cause of diarrheal disease in children in lower-income countries and among travelers. Here we investigate the potential role of MAIT cells in ETEC infection using blood samples from a controlled human challenge model with two ETEC strains, H10407 and B7A. On day 7 following challenge, MAIT cells exhibited an elevated activated phenotype accompanied by increased functionality and proliferation in peripheral blood, with the most pronounced pattern observed in individuals who developed moderate-to-severe diarrhea (MSD). This response was evident at both the protein and transcriptional levels. The MSD-positive group demonstrated elevated expression of CCR9 and α4β7 on MAIT cells, indicating increased homing potential to the gut mucosa. Additionally, this group experienced an expansion of the peripheral MAIT cell pool 28 d after the challenge. Interestingly, the initial expansion of the MAIT cell pool on day 7 post-challenge correlated with disease severity score. These findings indicate that MAIT cells can respond systemically with activation and expansion to ETEC infection, and that this response is associated with the development of symptomatic disease.