Mucosal-associated invariant T cells respond to colonic microbiome alterations during acute HIV infection

Mucosal-associated invariant T (MAIT) cells are an unconventional subset of T cells that respond to vitamin B2 metabolites from a range of bacteria and fungi. We have previously reported that peripheral MAIT cells are activated during acute HIV infection (AHI) in a manner associated with markers of microbial translocation. Here, we characterized peripheral and colonic MAIT cells from people with HIV (PWH) during AHI and after ART initiated during AHI or chronic HIV infection (CHI) and investigated their interplay with the colonic microbiome. During AHI, both peripheral and colonic MAIT cells were activated and showed evidence of proliferation. MAIT cell activation in blood and colon were unrelated to viral load and to each other, suggesting compartmentalized responses. Colonic CD4 MAIT cells were reduced and their reduction was associated with viral load, suggesting a direct viral effect. In vitro experiments confirmed that CD4 MAIT cells are susceptible to HIV-1 infection. Finally, changes in colonic microbiome composition were evident already during AHI and were associated with peripheral blood MAIT cell activation and effector maturation. Thus, these findings indicate that viral replication and colonic microbiome perturbation are associated with distinct, compartment-specific components of the MAIT cell response during AHI.