Work

Combinatorial action of TGFβ and IL-10 induces monocyte and monocyte-derived dendritic cell dysfunction in people living with HIV 3717

Year: 2025

Type: article

Abstract: Description People living with HIV (PWH) exhibit increased levels of platelet-monocyte complexes (PMCs). Differentiation of PMCs to dendritic cells (PMCDCs) in vitro resulted in reduced antigen uptake and expression of functionally important proteins. To investigate if anti-platelet drugs (APD: Clopidogrel, Aspirin) can rescue the immunogenicity of PMCDCs, platelets isolated from PWH (n = 6-8) and age/sex matched people without HIV (PWOH, n = 6-8) were treated with APD followed by activation using collagen. Platelets were then mixed with autologous monocytes which were differentiated into ΨHIV-pulsed mature DCs. Mixed effects analysis of platelet and PMCDC supernatants showed that platelets from PWH secreted higher levels of TGFβ which, in turn, polarized PMCDCs to also secrete higher levels of TGFβ. PMCDCs from PWH also secreted significantly higher levels of IL-10. CD4+ and CD8+ T cells stimulated by PMCDCs showed decreased proliferative capacity, which was rescued by APD in PWOH but not in PWH. These results indicate that increased interaction with platelets can induce TGFβ production by PMCDCs, while HIV infection can induce IL-10 production. The combinatorial immunosuppressive action of these two cytokines is irreversible by APD specifically in PWH. In conclusion, platelet mediated defects in DC function might underlie decreased endogenous anti-HIV immune responses, and the use of platelet-free monocytes as precursors for DC based vaccines might improve their immunostimulatory potential. Funding Sources Supported by: NIAID R21AI162076; URMC Intramural pilot funding TIIDIOP212344; NIAID T32AI007285 Topic Categories Viral Immunology (VIR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1485