Epithelium-innate immune cell axis in mucosal responses to SIV.
Epithelium-innate immune cell axis in mucosal responses to SIV.
复制标题
粘膜对SIV的粘膜反应中的上皮免疫细胞轴。
DOI：
10.1038/mi.2016.62
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发表时间：
2017-03
影响因子：
8
通讯作者：
Haase AT
中科院分区：
文献类型：
--
作者：
Shang L;Duan L;Perkey KE;Wietgrefe S;Zupancic M;Smith AJ;Southern PJ;Johnson RP;Haase AT
在HIV-1传播给女性的SIV-恒河猴模型中，暴露于高剂量SIV的粘膜反应的一个标志是CD 4 T细胞募集，其在早期感染中促进局部病毒扩增。在这项研究中，我们系统地分析了细胞的事件和化学引诱物的配置文件在宫颈组织之前的CD 4 T细胞募集。我们发现，阴道暴露于SIV接种物迅速诱导宫颈上皮细胞中的趋化因子表达，包括CCL 3，CCL 20和CXCL 8。趋化因子的表达与宫颈上皮下聚集的巨噬细胞和浆细胞样树突状细胞的早期募集有关。这些细胞产生的趋化因子CCL 3和CXCL 8又产生了与CD 4 T细胞募集空间相关的趋化因子梯度。我们进一步表明，SIVmac 239 Δnef疫苗接种对阴道攻击的保护作用与宫颈粘膜中不存在这种上皮-先天免疫细胞-CD 4 T细胞轴应答相关。我们的研究结果揭示了宫颈上皮细胞在启动阴道感染的早期粘膜反应中的关键作用，突出了巨噬细胞在靶细胞招募中的重要作用，并提供了保护性疫苗对这些早期粘膜反应的矛盾抑制作用的进一步证据。
In the SIV-rhesus macaque model of HIV-1 transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.