Peripheral blood CD4+CCR6+ compartment differentiates HIV-1 infected or seropositive elite controllers from long-term successfully treated individuals

HIV-1 infection induces a chronic inflammatory environment not restored by suppressive antiretroviral therapy (ART). As of today, the effect of viral suppression and immune reconstitution in people living with HIV-1 (PLWH) has been well described but not completely understood. Herein, we show how PLWH who naturally control the virus (PLWH_EC) have a reduced proportion of CD4⁺CCR6⁺and CD8⁺CCR6⁺cells compared to PLWH on suppressive ART (PLWH_ART) and HIV-1 negative controls (HC). Expression of CCR2 was reduced on both CD4⁺, CD8⁺and classical monocytes in PLWH_ECcompared to PLWH_ARTand HC. Longer suppressive therapy, measured in the same patients, decreased number of cells expressing CCR2 on all monocytic cell populations while expression on CD8⁺T cells increased. Furthermore, the CD4⁺CCR6⁺/CCR6⁻cells exhibited a unique proteomic profile with a modulated energy metabolism in PLWH_ECcompared to PLWH_ARTindependent of CCR6 status. The CD4⁺CCR6⁺cells also showed an enrichment in proteins involved in apoptosis and p53 signalling in PLWH_ECcompared to PLWH_ART, indicative of increased sensitivity towards cell death mechanisms. Collectively, this data shows how PLWH_EChave a unique chemokine receptor profile that may aid in facilitating natural control of HIV-1 infection.