Carias Ann M, Allen Shannon A, Fought Angela J, Kotnik Halavaty Katarina, Anderson Meegan R, Jimenez Maria L, McRaven Michael D, Gioia Casey J, Henning Tara R, Kersh Ellen N, Smith James M, Pereira Lara E, Butler Katherine, McNicholl S Janet M, Hendry R Michael, Kiser Patrick F, Veazey Ronald S, Hope Thomas J
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
PLoS Pathog. 2016 Sep 22;12(9):e1005885. doi: 10.1371/journal.ppat.1005885. eCollection 2016 Sep.
Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.
目前，越来越多的数据表明，某些激素避孕药的使用可能会影响女性感染HIV-1。然而，在非人类灵长类动物模型中，内源性或外源性孕激素占主导的状态显示会增加感染几率。为了深入了解这种感染几率增加的机制，我们研究了在天然孕激素存在的情况下，或者在注射高剂量醋酸甲羟孕酮（DMPA）后，黏膜屏障功能、CD4+ T细胞以及CD68+巨噬细胞的密度和定位是如何变化的。天然或注射的孕激素的存在增加了柱状上皮的病毒穿透以及易感细胞向阴道穹窿变薄的鳞状上皮的浸润，增加了潜在病毒与靶细胞相互作用的可能性。这些数据表明，内源性或外源性孕激素的增加都可能改变女性生殖道的屏障特性，并为孕激素水平升高时HIV-1感染风险增加提供了合理的机制。
