The MAIT conundrum - how human MAIT cells distinguish bacterial colonization from infection in mucosal barrier tissues

•MAIT cells are located in barrier tissues to perform front-line host defense.•MAIT cells in these tissues have increased pro-inflammatory transcripts (compared to blood) and are poised to respond rapidly.•A TCR signal is not sufficient for sustained MAIT cell effector function, which may prevent responses to commensal antigen.•Inflammatory cytokine signals synergize with the TCR signal to induce potent effector function.

We review the recent human mucosal-associated invariant T (MAIT) cell literature to examine the signals that control MAIT cell activation. We discuss these signals in context of MAIT cell function in mucosal barrier tissues and address how MAIT cells avoid responding to commensal bacteria, while maintaining responsiveness to infections.