Residual immune activation in HIV-Infected individuals expands monocytic-myeloid derived suppressor cells

Cell Immunol. 2021 Apr:362:104304. doi: 10.1016/j.cellimm.2021.104304. Epub 2021 Feb 10.

Abstract

HIV-infected individuals on combined antiretroviral therapy (ART) with virologic suppression exhibit sustained immune dysfunction. Our recent work has highlighted that monocytic myeloid derived suppressor cells (M-MDSC) are elevated in these individuals and suppress immune responses. Factors responsible for M-MDSC expansion in vivo are unknown. Here we compared circulating frequency of M-MDSC in HIV-infected persons from the US and India where HIV subtype-B or -C predominate, respectively. We further investigated soluble mediators of residual immune activation in two cohorts and determined their correlation with M-MDSC expansion. Our findings show that M-MDSC are elevated and correlate with plasma levels of IL-6 in both cohorts. Chemokines CXCL10, CCL4 and CXCL8 were also elevated in HIV-infected individuals, but did not correlate with M-MDSC. These findings support that IL-6 is important in M-MDSC expansion which is independent of HIV subtype.

Keywords: HIV; IL-6; Immune activation; Myeloid derived suppressor cells; People living with HIV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / pharmacology
  • Cells, Cultured
  • Disease Progression
  • Female
  • Gastrointestinal Microbiome / physiology
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • Humans
  • India / epidemiology
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism
  • United States / epidemiology

Substances

  • Anti-Retroviral Agents
  • Interleukin-6