Bouschbacher Marielle, Bomsel Morgane, Verronèse Estelle, Gofflo Sandrine, Ganor Yonatan, Dezutter-Dambuyant Colette, Valladeau Jenny
Claude Bernard Lyon 1 University, Centre Hospitalier Edouard Herriot, Lyon, France.
AIDS. 2008 Jul 11;22(11):1257-66. doi: 10.1097/QAD.0b013e3282f736f4.
The early steps of HIV entry into intact vaginal mucosa still need to be clarified. Here we investigated how HIV translocated across the vaginal pluristratified epithelium, either by transcytosis or by uptake in Langerhans cells.
Using human primary fibroblasts and vaginal epithelial cells, we developed an in-vitro model of vaginal mucosa in which Langerhans cells could also be integrated. Owing to the absence of T lymphocytes and macrophages, we specifically studied the role of Langerhans cells in HIV transmission and the transcytosis of cell-associated HIV.
Our model has a normal mucosal tissue architecture and Langerhans cells were efficiently integrated within the pluristratified epithelium. In addition, tight junction proteins' expression, high transepithelium resistance and low fluorescein isothiocyanate-BSA passage confirmed the integrity and impermeability of the reconstruction. Furthermore, we showed that human Langerhans cells also expressed tight junction proteins. Then, we demonstrated that neither transcellular nor intercellular transport of free infectious virus released by R5-infected or X4-infected peripheral blood mononuclear cells inoculated apically occured in the vaginal mucosa, irrespective to the presence of Langerhans cells.
For the first time, we documented that, within 4 h following contact with HIV-infected cells, translocation of free HIV particles across a pluristratified mucosa is not detectable and that, in this context, it seemed that Langerhans cells do not increase HIV transmission. Moreover, we provided a useful model for the development of strategies preventing HIV entry into the female genital tract, especially for testing the efficiency of various microbicides.
HIV进入完整阴道黏膜的早期步骤仍需阐明。在此，我们研究了HIV是如何通过跨细胞转运或被朗格汉斯细胞摄取而穿过阴道复层上皮的。
利用人原代成纤维细胞和阴道上皮细胞，我们建立了一种阴道黏膜体外模型，其中朗格汉斯细胞也可被整合。由于不存在T淋巴细胞和巨噬细胞，我们专门研究了朗格汉斯细胞在HIV传播以及细胞相关HIV跨细胞转运中的作用。
我们的模型具有正常的黏膜组织结构，朗格汉斯细胞有效地整合在复层上皮内。此外，紧密连接蛋白的表达、高跨上皮电阻和低异硫氰酸荧光素 - 牛血清白蛋白通过率证实了重建组织的完整性和不渗透性。此外，我们发现人朗格汉斯细胞也表达紧密连接蛋白。然后，我们证明，无论有无朗格汉斯细胞，经顶端接种的R5感染或X4感染的外周血单个核细胞释放的游离感染性病毒在阴道黏膜中既不发生跨细胞转运也不发生细胞间转运。
我们首次记录到，在与HIV感染细胞接触后的4小时内，未检测到游离HIV颗粒穿过复层黏膜的转运，并且在这种情况下，朗格汉斯细胞似乎不会增加HIV传播。此外，我们为开发预防HIV进入女性生殖道的策略提供了一个有用的模型，特别是用于测试各种杀菌剂的效果。
