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(EC) compared to PLWH(ART) and 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(EC) compared to PLWH(ART) independent of CCR6 status. The CD4(+)CCR6(+) cells also showed an enrichment in proteins involved in apoptosis and p53 signalling in PLWH(EC) compared to PLWH(ART), indicative of increased sensitivity towards cell death mechanisms. Collectively, this data shows how PLWH(EC) have a unique chemokine receptor profile that may aid in facilitating natural control of HIV-1 infection.