Grant: Project Grant

Most HIV infections are acquired through heterosexual intercourse, and in sub-Saharan Africa, 60% of new HIV infections affect women. Initial exposure to HIV-1 during sexual transmission occurs in the genital tract, however, little is known about HIV-1-specific immune responses at this site. We established an ongoing cohort of heavily HIV-1-exposed female commercial sex workers (CSWs), in Cotonou (Benin), in which we have identified individuals who remain HIV-1-uninfected (resistant) after more than 7 years of active prostitution. The fact that some individuals remain persistently seronegative despite high exposure to the virus such as the HIV-1-uninfected CSWs, implies that there are host factors that are highly protective. Our studies of the genital immune responses in CSWs suggest that resistance/control in the context of HIV-1 infection may be associated with the host's capacity to orchestrate dynamics of cellular populations to maintain low inflammatory conditions at the initial site of exposition. In the current study, we propose to characterize the cell populations as well as the cell signaling, immune and genetic factors that might be involved in generation of such inflammatory responses associated with protection against HIV-1 infection. The present study will provide a better understanding of the mechanisms of protection from HIV-1 infection and may help design strategies viewed to modulate mucosal inflammatory conditions, in order to establish a quick first line mucosal defense against HIV-1.