Susceptibility of Human Th17 Cells to Human Immunodeficiency Virus and Their Perturbation during Infection

Abstract

Background.Identification of the Th17 T cell subset as important mediators of host defense and pathology prompted us to determine their susceptibility to human immuno-deficiency virus (HIV) infection. Methods and results.We found that a sizeable portion of Th17 cells express HIV coreceptor CCR5 and produce very low levels of CCR5 ligands macrophage inflammatory protein (MIP)-1αand MIP-1β. Accordingly, CCR5⁺Th17 cells were efficiently infected with CCR5-tropic HIV and were depleted during viral replication in vitro. Remarkably, HIV-infected individuals receiving treatment had significantly reduced Th17 cell counts, compared with HIV-uninfected subjects, regardless of viral load or CD4 cell count, whereas treatment-naive subjects had normal levels. However, there was a preferential reduction in CCR5⁺T cells that were also CCR6 positive, which is expressed on all Th17 cells, compared with CCR6⁻CCR5⁺cells, in both treated and untreated HIV-infected 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-infected individuals who are receiving treatment. Conclusions.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.