TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells
TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells
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DOI：
10.1073/pnas.0907347106
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发表时间：
2009-09-29
影响因子：
11.1
通讯作者：
Sastry, K. Jagannadha
中科院分区：
文献类型：
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作者：
Fontenot, Danielle;He, Hong;Sastry, K. Jagannadha
粘多糖树突状细胞参与HIV向CD 4（+）T细胞的捕获、储存和传播，以及在同源T细胞和DC相互作用期间促进HIV在活化的CD 4（+）T细胞中的复制。我们报道了HIV通过激活NF κ B B信号通路诱导人生殖道粘膜上皮细胞产生胸腺基质淋巴细胞生成素（TSLP）。HIV暴露的上皮细胞分泌的TSLP激活DC，促进共培养的自体CD 4（+）T细胞增殖和HIV-1复制。在恒河猴中，我们观察到阴道SIV暴露后的前2周内TSLP表达显著增加，同时阴道组织中病毒复制增加。这些数据表明，粘膜上皮细胞产生的HIV介导的TSLP是DC介导的活化CD 4（+）T细胞中HIV感染扩增的关键触发因素。由HIV诱导的TSLP介导的粘膜上皮细胞与DC之间的相互作用可能是女性通过阴道粘膜高感染率的重要机制。
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 NF kappa B 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.