Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells.
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 pro-inflammatory profile in monocyte-derived cytokines, but not in lymphocyte-derived cytokines. Particularly, the production of the IL-1beta to imiquimod, E. coli LPS and Mycobacterium tuberculosis was increased, and this production correlated with plasma concentrations of hsCRP and sCD14. This increase in monocyte responsiveness remained stable over time in subsequent blood sampling after >1year. Transcriptome analyses confirmed priming of the monocyte IL-1beta pathway, consistent with a monocyte trained immunity phenotype. Increased plasma concentrations of beta-glucan, a well-known inducer of trained immunity, were associated with increased innate cytokine responses. Monocytes of PLHIV exhibit a sustained pro-inflammatory immune phenotype with priming of the IL-1beta 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.
|Authors:||van der Heijden WA, van de Wijer L, Keramati F, Trypsteen W, Rutsaert S, Ter Horst R, Jaeger M, Koenen HJ, Stunnenberg HG, Joosten I, Verweij PE, van Lunzen J, Dinarello CA, Joosten LA, Vandekerckhove L, Netea MG, van der Ven AJ, de Mast Q,|
|Journal:||JCI Insight; 2021 Apr 8;6(7):145928. doi:10.1172/jci.insight.145928|
|PubMed:||PMID: 33630761 (Go to PubMed)|