IMMUNOMODULATORY PROPERTIES OF SEMINAL VESICLES CONTENT: IMPACT ON IMMUNE RESPONSE AGAINST HSV-2

A. VARESE; F. REMES LENICOV; G. ERNST; A. MERLOTTI; E. DANTAS; F. ERRA DÍAZ; J. RUBIONE; G. DUETTE; P. PEREYRA GERBER; J. GEFFNER; A. CEBALLOS

Mar del Plata

Conferencia; Reunión anual SAI-SAIC; 2014

Sociedad Argentina de Inmunología

Semen is the main vector of a wide range of sexually transmitted infectious diseases. In addition, it is able to induce significant immunosuppressive actions that favor alo-reactive tolerance to paternal antigens. Our hypothesis is that semen, beyond being a vehicle of infectious agents, has the ability to modulate the immune response against sexually transmitted pathogens. Six- to 8-week-old female Balb/C mice, previously injected (sc) with progesterone, were inoculated ivag. with HSV-2 in the presence or absence of seminal vesicles content (VS). Another group of mice were vaccinated ivag. with inactivated HSV-2 in the presence or absence of VS, and a month later challenged with a letal dose of HSV-2. VS was extracted post mortem from 10-12 week-old male Balb/C mice and pooled. Virus titers in vaginal fluids and spinal cord were measured by PFU method. Iliac lymph nodes, spleen and genital mucosa cells were washed and used to measure TNF-α, IL-17, IL-6, IL-10 or IFN-γ in cells supernatants by ELISA, and IFN-γ producing cells by ELISPOT. TGF-β, IL-10, CCL2, CCL5, CXCL9 and CXCL10 expression in these cells was analyzed by RT-qPCR and main cell populations were characterized by flow cytometry: T CD4+, T CD8+, T CD4+CD25+FOXP3, CD11c, CD11b, Ly6g and NK. IgG and IgA in blood and vaginal fluids were quantified by ELISA. When analyzing the primary infection, no significant differences were found in clinical progression and survival between groups. However, mice infected with VS showed lower viral titers in vaginal washes at day 3 pi (n=20 p<0.05), and an increase IFN-γ production in spleen cells at day 10 pi (n=10 p<0.01). In the vaccinated mice, those immunized in the presence of VS showed a 90% survival compared to the control group 10% (n=20), and minor sings of disease. We also observed an increased IFN-γ production (n=20 p<0.05), augmented presence of T CD8+ cells at the site of infection (n=20 p<0.05), and an increased CXCL9 production (n=10 p<0.05) at day 3 pi in the group vaccinated in the presence of VS. Our results suggest that VS increases IFN-γ mediated mechanisms against HSV-2 infection, promoting strong specific immune response to new challenges with the virus.