Objectives: Although more than 60% of HIV transmission occurs via semen, little is known about the immune impact of seminal plasma on HIV susceptibility. Here, we examined the level of selected immunomodulatory factors in seminal plasma from HIV-uninfected and therapy-naive, HIV-infected men in acute and chronic stages; the cytokine response elicited by seminal plasma in genital epithelial cells (GECs); and whether any GEC response to seminal plasma could drive HIV replication in infected T cells.
Methods: A panel of nine cytokines and chemokines was measured in seminal plasma from HIV-uninfected and HIV-infected men and in primary GEC cultures following seminal plasma exposure. HIV-long terminal repeat (LTR) activation was measured in 1G5 T cells exposed to supernatants from seminal plasma-treated GECs.
Results: Pro-inflammatory cytokines and chemokines were present at significantly higher levels in seminal plasma from acute men, whereas transforming growth factor (TGF)-β1 was significantly higher in seminal plasma from chronic men. Pro-inflammatory cytokine production by GECs was significantly decreased following incubation with seminal plasma from chronic men. Blocking the TGF-β1 receptor in GECs prior to seminal plasma exposure enhanced pro-inflammatory cytokine production. Exposure to seminal plasma activated nuclear factor (NF)-κB in GECs and blocking it significantly reduced pro-inflammatory cytokine production. GEC responses to seminal plasma, especially from acute men, significantly activated HIV-LTR activation in 1G5 T cells.
Conclusion: Immunomodulatory factors in seminal plasma vary, depending on presence and stage of HIV infection. Exposure to seminal plasma leads to NF-κB activation and pro-inflammatory cytokine production, whereas TGF-β in seminal plasma may suppress pro-inflammatory cytokine production by GECs. GEC responses to seminal plasma can activate HIV-LTR in infected CD4(+) T cells.