Plasma Derived Extracellular Vesicles Modulate Monocyte IL-18, IFN-α and IL-10 responses in Adults with HIV-related Cognitive Impairment

Abstract Background: HIV-associated neurocognitive dysfunction persists despite suppressive antiretroviral therapy (ART). Extracellular vesicles (EVs) are emerging modulators of immunological responses. We have previously shown that EVs expressing monocyte activation and neuronal markers associated with HIV cognitive impairment (CI). Whether these EV changes observed in people (PWH) influence innate cellular function among those CI remains unclear. Method: Purified samples from 58 HIV-infected individuals on ART either (CI, n=48) or normal cognition (NC, n=10) 8 uninfected controls were isolated using differential centrifugation co-cultured PBMCs a single donor for 18 hrs. Eight intracellular cytokines 13 surface chemokines myeloid differentiation assessed by spectral flow cytometry. Non-parametric statistical T tests used. Result: Monocytes (mono) showed effects multiple cytokine responses cell receptors after exposure to without CI. Levels mono IL-18 significantly lower incubation derived compared controls. Based status, HIV-CI group % IFN-α higher IL-10 per basis when the NC group. Conclusion: These results suggest can modulate irrespective status. PWH exhibited altered driven Our data support interventions target reverse restore perturbations limit neuropathology ART. Supported grants NIH (R21NS106970 R01NS117458)