Human Th 17 cells are susceptible to HIV and are perturbed during infection

Background—Identification of the Th17 T cell subset as important mediators of host defense and pathology, prompted us to determine their susceptibility to HIV infection. Methods and Results—We found that a sizeable portion of Th17 cells express HIV co-receptor CCR5 and produce very low levels of CCR5 ligands MIP-1α and MIP-1β. Accordingly, CCR5+ Th17 cells were efficiently infected with CCR5-tropic HIV and were depleted during viral replication in vitro. Remarkably, HIV+ individuals under treatment showed significantly reduced Th17 cells compared to HIV− subjects, regardless of their viral loads or CD4 numbers, whereas treatment naïve subjects had normal levels. However, there was a preferential reduction in CCR5+ T cells that were also CCR6+, which is expressed on all Th17 cells, as compared to CCR6−CCR5+ cells, in both treated and untreated HIV+ subjects. This observation suggests preferential targeting of CCR6+CCR5+ Th17 cells by CCR5-tropic viruses in vivo. Th17 cell levels also inversely correlated with activated CD4+ T cells in HIV+ individuals under treatment. Conclusion—Our findings suggest a complex perturbation of Th17 subsets during the course of HIV-disease potentially through both direct viral infection and virus indirect mechanisms such as immune activation.