Abstract
Africa accounts for the majority of global human immunodeficiency virus (HIV) infections, most of which affect women through heterosexual intercourse. Currently, there is no cure for HIV and the development of vaccines and microbicides remains the best solution to eradicate the pandemic. We and others have identified HIV highly-exposed seronegative (HESN) individuals among African female commercial sex workers (CSWs). Analyses of genital samples from HESNs have demonstrated potent innate and anti-inflammatory conditions, HIV-specific CD4+ and CD8+ T-cells as well as immunoglobulins (Igs), and increased regulatory cell populations, all of which support a delicate balance between strength and control against HIV intrusion. Moreover, we have recently shown that frequencies of innate marginal zone (MZ) B-cells are decreased in the blood of HESNs when compared to HIV-uninfected non-CSW women, suggesting their recruitment to peripheral sites. This coincides with the fact that levels of B lymphocyte stimulator (BLyS/BAFF), known to shape the MZ pool and whose overexpression leads to MZ deregulation in HIV-infected progressors, are significantly lower in the blood of HESNs when compared to both HIV-infected CSWs and HIV-uninfected non-CSW women. Interestingly, MZ B-cells can bind HIV gp120 and produce specific IgG and IgA, and have a propensity for B regulatory potential, which could help both the fight against HIV and maintenance of low inflammatory conditions in HESNs. HESN individuals provide an exceptional opportunity to identify important clues for the development of protective devices, and efforts should aim at soliciting immune responses observed in the context of their natural immunity to HIV.
Highlights
Worldwide, it is estimated that nearly 36.7 million people live with human immunodeficiency virus (HIV)
Individuals highly exposed to HIV and persistently seronegative (HESN) have been shown to possess low-inflammatory conditions and immune responsiveness towards the virus [2,3,4], which suggests that the capacity to maintain a low-key inflammatory profile along with anti-HIV responses is associated with protection
We recently reported that endocervical myeloid HLA-DR+ cells from Beninese HESN commercial sex workers (CSWs) expressed higher levels of IFN-α, toll-like receptors (TLRs) 7, IL-10 and HLA-G than those from both HIV-infected CSWs and HIV-uninfected non-CSWs
Summary
It is estimated that nearly 36.7 million people live with human immunodeficiency virus (HIV). The transmission mechanisms of the virus and immune responsiveness at the initial site of infection are not fully understood. Frequent mucosal exposure to HIV in the absence of infection was documented in different cohorts, including the Beninese commercial sex workers (CSWs) [2]. Individuals highly exposed to HIV and persistently seronegative (HESN) have been shown to possess low-inflammatory conditions and immune responsiveness towards the virus [2,3,4], which suggests that the capacity to maintain a low-key inflammatory profile along with anti-HIV responses is associated with protection. Viruses 2018, 10, 215 against HIV infection.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
