Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells

JCI Insight. 2021 Apr 8;6(7):e145928. doi: 10.1172/jci.insight.145928.


Chronic inflammation and immune dysfunction play a key role in the development of non-AIDS-related comorbidities. The aim of our study was to characterize the functional phenotype of immune cells in people living with HIV (PLHIV). We enrolled a cross-sectional cohort study of PLHIV on stable antiretroviral therapy and healthy controls. We assessed ex vivo cytokine production capacity and transcriptomics of monocytes and T cells upon bacterial, fungal, and viral stimulation. PLHIV exhibited an exacerbated proinflammatory profile in monocyte-derived cytokines, but not in lymphocyte-derived cytokines. Particularly, the production of the IL-1β to imiquimod, E. coli LPS, and Mycobacterium tuberculosis was increased, and this production correlated with plasma concentrations of high-sensitivity C-reactive protein and soluble CD14. This increase in monocyte responsiveness remained stable over time in subsequent blood sampling after more than 1 year. Transcriptome analyses confirmed priming of the monocyte IL-1β pathway, consistent with a monocyte-trained immunity phenotype. Increased plasma concentrations of β-glucan, a well-known inducer of trained immunity, were associated with increased innate cytokine responses. Monocytes of PLHIV exhibited a sustained proinflammatory immune phenotype with priming of the IL-1β pathway. Training of the innate immune system in PLHIV likely plays a role in long-term HIV complications and provides a promising therapeutic target for inflammation-related comorbidities.

Keywords: AIDS/HIV; Immunology; Innate immunity; Monocytes; Transcription.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Case-Control Studies
  • Chronic Disease
  • Cytokines / genetics
  • Cytokines / immunology
  • Female
  • Gene Expression
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • Humans
  • Immunity, Innate / genetics*
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / virology
  • Interleukin-1beta / blood*
  • Interleukin-1beta / genetics
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / virology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • beta-Glucans / metabolism


  • Anti-HIV Agents
  • Cytokines
  • IL1B protein, human
  • Interleukin-1beta
  • Lipopolysaccharides
  • beta-Glucans