Purpose of review
This review highlights current knowledge on the dichotomous role played by T helper 17 cells (Th17)-polarized CD4+ T cells in maintaining mucosal immunity homeostasis versus fueling HIV/simian immunodeficiency virus (SIV) replication/persistence during antiretroviral therapy (ART), with a focus on molecular mechanisms underlying these processes.
Th17 cells bridge innate and adaptive immunity against pathogens at mucosal barrier surfaces. Th17 cells are located at portal sites of HIV/SIV entry, express a unique transcriptional/metabolic status compatible with viral replication, and represent the first targets of infection. The paucity of Th17 cells during HIV/SIV infection is caused by infection itself, but also by an altered Th17 differentiation, survival, and trafficking into mucosal sites. This causes major alterations of mucosal barrier integrity, microbial translocation, and disease progression. Unless initiated during the early acute infection phases, ART fails to restore the frequency/functionality of mucosal Th17 cells. A fraction of Th17 cells is long-lived and carry HIV reservoir during ART. Recent studies identified Th17-specific host factors controlling HIV transcription, a step untargeted by current ART.
The identification of molecular mechanisms contributing to HIV replication/persistence in mucosal Th17 cells paves the way toward the design of new Th17-specific therapeutic strategies aimed at improving mucosal immunity in HIV-infected individuals.