Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

International audienceBACKGROUND: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen

Systemic immune modulation using chemokine receptor 7 expressing porcine Sertoli cells

BACKGROUND: Sertoli cells (SC) are known to have active mechanism for evading humoral immune response and are known to have immune modulatory effects in the presence of other antigens. This has led us to hypothesize that systemic immune modulating effect of SC might be optimized by their residence on peripheral lymph node. This study was designed to evaluate our new strategy to promote preventive or therapeutic effects of SC in systemic immune modulation for organ transplantation. METHODS: For this purpose, we created chemokine receptor 7 (CCR7) expressing porcine SC (NPSCi-CCR7) to facilitate their migration into lymphoid organ in vivo and their potential to modulate systemic immune responses was evaluated using mouse allogeneic skin graft model. RESULTS: Directed migration of NPSCi-CCR7 cells from periphery into lymphoid organs was dramatically promoted compared to control NPSCi cells. Also pre-transplantation of NPSCi-CCR7 significantly suppressed lymphocyte proliferation and prolonged the allogeneic skin graft survival. CONCLUSION: These results suggest that our new strategy to traffic SC to lymphoid organs using CCR7 is very effective and can be extended to traffic other immune modulatory cells or proteins to primary and secondary lymphoid structures to augment their therapeutic potential