Gastrointestinal MAIT cells in chronic HIV-1 infection

Mucosa-associated invariant T (MAIT) cells are innate-like T cells abundant in mucosal tissues, liver, and blood. MAIT cells recognize riboflavin metabolite-derived microbial antigens displayed by the MHC-I-related protein (MR1) and respond by producing cytokines, killing infected cells, and suppressing microbial growth. We previously demonstrated that MAIT cell numbers and function are reduced in chronic HIV-1, potentially increasing susceptibility to microbial coinfections. Here we assessed colorectal MAIT cells from people living with HIV-1 (PLWH, n = 36) and people without HIV-1 (PWOH, n = 22) by flow cytometry. In PBMCs, MAIT cells were less abundant in PLWH compared to PWOH. However, colorectal MAIT cell percentages were comparable in both groups, suggesting reduced loss from gut compared to blood in HIV-1 infection, or redistribution from blood to mucosae. In both groups, the majority of mucosal MAIT cells expressed CD8 and were enriched for CD8αα; a minority expressed CD4 or were double negative. Colorectal MAIT cells expressed CD69 and CD45RO, indicating a tissue-resident memory phenotype. Mucosal MAIT cells from PWOH expressed high perforin compared to PLWH, although granzyme B was low as compared to blood counterparts. Intracellular cytokine staining revealed robust cytokine production when stimulated with PMA/ionomycin. However, while blood MAIT cells responded strongly to inactivated Escherichia coli, mucosal MAIT cells responded poorly to this stimulus. Thus, gastrointestinal MAIT cells may be partially unresponsive toward commensal microbes, while remaining responsive to other stimuli. These findings provide novel insights into the functional profile of gastrointestinal MAIT cells in the context of chronic HIV-1.