Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques.
Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques.
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DOI：
10.1016/j.chom.2016.03.005
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发表时间：
2016-04-13
影响因子：
30.3
通讯作者：
Hope TJ
中科院分区：
文献类型：
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作者：
Stieh DJ;Matias E;Xu H;Fought AJ;Blanchard JL;Marx PA;Veazey RS;Hope TJ
在黏膜感染艾滋病毒后立即检测罕见的受感染细胞存在困难，这阻碍了我们对该病毒最初靶向细胞的了解。利用猕猴 - 猴免疫缺陷病毒（SIV）阴道感染模型，我们开发了一种方法，可在阴道接种48小时后识别出SIV（mac239）感染的离散病灶。我们在从阴唇到卵巢的整个生殖道中都发现了感染病灶。对受感染细胞进行表型分析显示，SIV明显倾向于感染CCR6 + CD4 + T细胞。感染SIV的细胞表达转录调节因子RORγt，这证实了最初的靶细胞明确属于Th17谱系。此外，我们检测到了宿主对感染的反应，表现为受感染细胞的凋亡、细胞裂解和吞噬作用。因此，我们的分析确定Th17谱系的CCR6 + CD4 + T细胞是阴道传播过程中SIV的主要靶细胞。这为采取干预措施保护这些细胞并预防艾滋病毒传播提供了新的机会。
The difficulty in detecting rare infected cells immediately after mucosal HIV transmission has hindered our understanding of the initial cells targeted by the virus. Working with the macaque-simian immunodeficiency virus (SIV) vaginal challenge model, we developed methodology to identify discrete foci of SIV (mac239) infection 48 hours after vaginal inoculation. We find infectious foci throughout the reproductive tract, from labia to ovary. Phenotyping infected cells reveals that SIV has a significant bias for infection of CCR6+ CD4+ T cells. SIV infected cells expressed the transcriptional regulator RORγt confirming that the initial target cells are specifically of the Th17 lineage. Furthermore, we detect host responses to infection, as evidenced by apoptosis, cell lysis, and phagocytosis of infected cells. Thus, our analysis identifies Th17 lineage CCR6+ CD4+ T cells as primary targets of SIV during vaginal transmission. This opens new opportunities for interventions to protect these cells and prevent HIV transmission.