Étude de l’immunité mucosale génitale chez des femmes béninoises hautement exposées au VIH-1 séronégatives (HESN) et séropositives
Background: Today, 35.3 million people live with human immunodeficiency virus (HIV)-1; and 70% of infections occur in sub-Saharan Africa, mostly through heterosexual intercourse and mainly affect women. The female genital tract (FGT) has a complex immune milieu that has to deal with invading pathogens while maintaining tolerance/control of the vagina microflora and being under the influence of sex hormones. Also, mechanisms favouring or preventing HIV infection of the FGT are not well identified. Hypothesis: The inflammatory environment and the outcome of crosstalk between epithelial genital cells (EGC) and the myeloid dendritic cells, which are of the first to encounter the virus at mucosal ports of entry, modulate lymphocytes activities that will be determinant in the type of immune response elaborated by the host. Methods: The samples obtained from women enrolled in a cohort of commercial sex workers (CSW) in Cotonou, Benin in sub-Saharan Africa were analyzed. We have characterized the female genital mucosal milieu of HIV-1 highly exposed seronegative (HESN) CSWs and have compared it with that of HIV-1 infected CSWs. Briefly, cervico-vaginal liquids were determined by multiplex/Luminex technologies or by ELISA and cells were described following flow cytometry analysis (phenotyping and cell sorting). Results: Our observations allow us to shed light on a potential natural immune protection mechanism in the HESN CSWs group. We have identified high levels of the antiviral, immunomodulatory and antiproliferative soluble cytokine interferon (IFN)-α in the FGT of the HESN CSWs group. The high levels of IFN-α suggested the possible existence of critical cell crosstalks that would favour the control of the genital immune compartment in the restriction of HIV-1 infection. The study of molecules involved in IFN-α signaling pathways in the EGC and in myeloid cells, show the presence of a «tolerogenic/regulatory» microenvironment. Furthermore, we have characterized for the first time a population of myeloid cells presenting features of «tolerogenic DC» in the FGT of HESN CSWs, and which express interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4. Conclusion : This study will have major impact on the development of preventive intervention strategies viewed to modulate preexisting inflammatory conditions, and establishing mucosal defence that will be held rapidly and will be long-lasting against the HIV-1 infection.
HESN HIV-1 innate and adaptive mucosal genital immunity tolerogenic/regulator microenvironment