Semen exosomes inhibit HIV infection and HIV-induced proinflammatory cytokine production independent of the activation state of primary lymphocytes.

Semen exosomes (SE) inhibit HIV infection. However, the effect of SE on cell activation and inflammation remains unknown. We characterized the response of peripheral blood mononuclear cells (PBMCs) from HIV-uninfected and antiretroviral therapy-suppressed HIV-infected (HIV+) subjects to SE. Quiescent PBMCs or T-cell receptor (TCR)-activated PBMCs from HIV- and HIV+ donors were stimulated with SE in the presence/absence of ex vivo HIV infection. In HIV-infected PBMCs, SE did not reactivate HIV, did not induce lymphoblast development, nor increase CD69+/CD25+ numbers. Furthermore, SE inhibited de novo HIV infection without altering cell activation. SE also asynchronously downregulated HIV-inducible IL1β, IL8, and TNFα and upregulated CXCL10. These data suggest that SE inhibits HIV infection and production of HIV-induced proinflammatory cytokines while preserving lymphocyte activation.