Spermatozoa efficiently transmit HIV-1 to dendritic cells and elicit their phenotypic maturation

REMES LENICOV, FEDERICO; RODRÍGUEZ RODRÍGUES, CHRISTIAN; CABRINI, MERCEDES; SABATTE, JUAN; JANCIC, CAROLINA; DONALDSON, M; PASQUALINI (H), R. A.; GEFFNER, JORGE; CEBALLOS, ANA

Buenos Aires

Workshop; 3rd ICGEB Workshop on Human RNA Viruses; 2012

Semen is the main vector for HIV-1 dissemination. Previously we have shown that spermatozoa are capable of capturing HIV-1 through heparan sulfate glycoproteins present on their surface. In this study, we hypothesized that spermatozoa could transmit the attached virus to dendritic cells (DCs). Furthermore, we also hypothesized that the presence of spermatozoa in the transmission event influences the immunologic response mounted by the DCs. Spermatozoa were purified from healthy subjects by gradient centrifugation. Purified spermatozoa were incubated with HIV-1 (BaL and IIIB strains), then washed to remove free virus, and finally co-cultured with monocyte-derived DCs. After 7 days, the amount of HIV-1 produced by DCs was analyzed by measuring p24 antigen by ELISA. DC phenotype was studied by flow cytometry and cytokine production by ELISA. We found that DCs were infected with HIV-1 after co-culture with HIV-1-loaded spermatozoa. However, DCs remained uninfected when spermatozoa and DCs were placed in different chambers of a transwell system, indicating that transmission required cell-to-cell contact. Fluorescence, confocal and electronic microscopy showed internalization of a fraction of the spermatozoa by DCs during co-cultures. This interaction also resulted in the phenotypic maturation of DCs (up-regulation of CD80, CD86, CD40, CD83 and CCR7). Interestingly, interaction with spermatozoa triggered production of IL-10 but not IL-12p70. We conclude that spermatozoa can transmit HIV-1 to DCs and simultaneously modulate their response. All in all, these observations support the notion that far from being a passive carrier, spermatozoa might affect the early course of sexual transmission of HIV-1 infection.