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

• Published in: Communications biology 2022-04, Vol.5 (1), p.357-357, Article 357
• Main Authors: Svensson Akusjärvi, Sara, Krishnan, Shuba, Jütte, Bianca B., Ambikan, Anoop T., Gupta, Soham, Rodriguez, Jimmy Esneider, Végvári, Ákos, Sperk, Maike, Nowak, Piotr, Vesterbacka, Jan, Svensson, J. Peter, Sönnerborg, Anders, Neogi, Ujjwal
• Format: Article
• Language: English
• Subjects: 13/21; 45/77; 631/250/254; 692/699/255/1901; 82/1; 82/58; 96/31; Antiretroviral therapy; Apoptosis; Biology; Biomedical and Life Sciences; CC chemokine receptors; CCR2 protein; CCR6 protein; CD4 antigen; CD4-Positive T-Lymphocytes; CD8 antigen; CD8-Positive T-Lymphocytes; Cell death; Chemokine receptors; Chemokines; Chronic infection; Drug therapy; Elite Controllers; Energy metabolism; HIV; HIV Infections - drug therapy; HIV-1; Human immunodeficiency virus; Humans; Immune reconstitution; Infections; Inflammation; Life Sciences; Lymphocytes T; Medicin och hälsovetenskap; Monocyte chemoattractant protein 1; Monocytes; p53 Protein; Peripheral blood; Proteomics; Receptors, CCR6 - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03315-x

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. The expression profiles dynamics of several chemokine receptors are lower for people living with HIV-1 who naturally control the virus compared to those on suppressive antiretroviral therapy and HIV-negative controls, shedding light on the mechanisms of natural control of HIV-1 infection.