Fontenot Danielle, He Hong, Hanabuchi Shino, Nehete Pramod N, Zhang Minying, Chang Mikyoung, Nehete Bharti, Wang Yui-Hsi, Wang Yi-Hong, Ma Zhong-Min, Lee Hai-Chon, Ziegler Steven F, Courtney Amy N, Miller Christopher J, Sun Shao-Cong, Liu Yong-Jun, Sastry K Jagannadha
Departments of Immunology and Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA.
Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16776-81. doi: 10.1073/pnas.0907347106. Epub 2009 Sep 21.
Mucosal dendritic cells have been implicated in the capture, storage, and transmission of HIV to CD4(+) T cells as well as in the promotion of HIV replication in activated CD4(+) T cells during the cognate T-cell and DC interaction. We report that HIV induces human genital mucosal epithelial cells to produce thymic stromal lymphopoietin (TSLP) via activation of the NFkappaB signaling pathway. The TSLP secreted by HIV exposed epithelial cells activated DC, which promoted proliferation and HIV-1 replication of co-cultured autologous CD4(+) T cells. In rhesus macaques, we observed dramatic increases in TSLP expression concurrent with an increase in viral replication in the vaginal tissues within the first 2 weeks after vaginal SIV exposure. These data suggest that HIV-mediated TSLP production by mucosal epithelial cells is a critical trigger for DC-mediated amplification of HIV-infection in activated CD4(+) T cells. The cross talk between mucosal epithelial cells and DC, mediated by HIV-induced TSLP, may be an important mechanism for the high rate of HIV infection in women through the vaginal mucosa.
黏膜树突状细胞与HIV捕获、储存及向CD4(+) T细胞的传递有关，也与同源T细胞和树突状细胞相互作用期间活化的CD4(+) T细胞中HIV复制的促进有关。我们报告，HIV通过激活NFκB信号通路诱导人泌尿生殖黏膜上皮细胞产生胸腺基质淋巴细胞生成素（TSLP）。HIV感染的上皮细胞分泌的TSLP激活树突状细胞，促进共培养的自体CD4(+) T细胞增殖和HIV-1复制。在恒河猴中，我们观察到阴道暴露于SIV后的头2周内，阴道组织中TSLP表达显著增加，同时病毒复制也增加。这些数据表明，黏膜上皮细胞由HIV介导产生TSLP是树突状细胞介导的活化CD4(+) T细胞中HIV感染扩增的关键触发因素。由HIV诱导的TSLP介导的黏膜上皮细胞与树突状细胞之间的相互作用，可能是女性通过阴道黏膜感染HIV的高发生率的重要机制。
