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The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-β-estradiol (E2) and ethinyl estradiol (EE) in HIV-infection of CD4+ T-cells and macrophages. Purified CD4+ T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4+ T-cells and macrophages with E2 prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E2 2 h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E2 and had no effect on CD4+ T-cell infection. Reduction of HIV-infection induced by E2 in CD4+ T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E2. In macrophages, despite the lack of an effect of E2 on CCR5 expression, E2–treatment reduced viral entry 2 h after challenge and increased MIP-1β secretion. These results demonstrate the direct effect of E2 on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms. [ABSTRACT FROM AUTHOR]

Women acquire HIV through sexual transmission. Women worldwide represent half of the people living with HIV, but young women in endemic areas are disproportionally affected. Low transmission rates per sexual act in women suggest that local immune protective mechanisms in the genital tract have the potential to prevent infection. However, conditions that induce genital inflammation are known to increase the risk of HIV acquisition. The female genital tract (FGT) is divided into different anatomical compartments with distinct reproductive functions. The immune cells present in each of these compartments are specialized in balancing reproduction and protection against infections, and are the same cells that can encounter and respond to HIV. Understanding the physiological and pathological factors that influence mucosal immune cell presence, susceptibility to HIV-infection and anti-HIV immune responses in the FGT is necessary to develop preventive strategies. Here we review recent advances in our understanding of HIV infection in the human female genital tract, with an emphasis on the characterization of the mucosal cells susceptible to HIV-infection, innate immune responses and mucosal factors that increase genital inflammation and influence susceptibility to HIV acquisition in women., Competing Interests: Conflict of interested statement. Nothing declared.

As women age, susceptibility to systemic and genital infections increases. Tissue-resident memory T cells (TRMs) are CD103 + CD8 + long-lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8 + T cells. While CD103 + CD8 + T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103 + CD8 + T cells were increased in postmenopausal compared to premenopausal women. Endometrial DCs from postmenopausal women were significantly more effective at inducing CD103 expression on allogeneic naïve CD8 + T cells than DCs from premenopausal women; CD103 upregulation was mediated through membrane-bound TGFβ signaling. In contrast, cervical CD103 + T cells and DC numbers declined in postmenopausal women with age. Decreases in DCs correlated with decreased CD103 + T cells in endocervix, but not ectocervix. Our findings demonstrate a previously unrecognized compartmentalization of TRMs in the FRT of postmenopausal women, with loss of TRMs and DCs in the cervix with aging, and increased TRMs and DC induction capacity in the endometrium. These findings are relevant to understanding immune protection in the FRT and to the design of vaccines for women of all ages., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)