Endometrial epithelial cell response to semen from HIV-infected men during different stages of infection is distinct and can drive HIV-1-long terminal repeat
Endometrial epithelial cell response to semen from HIV-infected men during different stages of infection is distinct and can drive HIV-1-long terminal repeat
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DOI：
10.1097/qad.0b013e32834e57b2
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发表时间：
2012-01-02
期刊：
影响因子：
3.8
通讯作者：
Kaushic, Charu
中科院分区：
文献类型：
--
作者：
Kafka, Jessica K.;Sheth, Prameet M.;Kaushic, Charu
目的：虽然超过60%的HIV通过精液传播，但精浆对HIV易感性的免疫影响知之甚少。在这里，我们检测了急性期和慢性期HIV未感染和未接受治疗的HIV感染男性精浆中特定免疫调节因子的水平；精浆在生殖器上皮细胞(GEC)中引发的细胞因子反应；以及精浆对精浆的反应是否可以推动HIV在感染T细胞中的复制。方法：检测HIV未感染和HIV感染男性精浆中的9种细胞因子和趋化因子，以及精浆暴露后GEC原代培养中的9种细胞因子和趋化因子。结果：急性期患者精浆中促炎症细胞因子和趋化因子水平明显高于慢性患者，而慢性患者精浆中转化生长因子-β1水平明显升高。在与慢性男性精浆孵育后，GEC产生的促炎细胞因子显著减少。在精浆暴露前阻断GEC中的转化生长因子-β1受体可促进促炎细胞因子的产生。在GEC中暴露于精浆激活的核因子-kappa B并将其阻断，可显著减少促炎细胞因子的产生。GEC对精浆，尤其是急性男性精浆的反应，显著激活了1G5T细胞中HIV-LTR的激活。结论：精浆中的免疫调节因子因HIV感染的存在和阶段而异。暴露于精浆中会导致核因子-kappaB的激活和促炎细胞因子的产生，而精浆中的转化生长因子-β可能会抑制促炎症细胞因子的产生。GEC对精浆的反应可以激活感染的CD4(+)T细胞中的HIV-LTR。(C)2011年Wolters Kluwer Health垂直酒吧Lippincott Williams&Wilkins
Objectives: Although more than 60% of HIV transmission occurs via semen, little is known about the immune impact of seminal plasma on HIV susceptibility. Here, we examined the level of selected immunomodulatory factors in seminal plasma from HIV-uninfected and therapy-naive, HIV-infected men in acute and chronic stages; the cytokine response elicited by seminal plasma in genital epithelial cells (GECs); and whether any GEC response to seminal plasma could drive HIV replication in infected T cells.Methods: A panel of nine cytokines and chemokines was measured in seminal plasma from HIV-uninfected and HIV-infected men and in primary GEC cultures following seminal plasma exposure. HIV-long terminal repeat (LTR) activation was measured in 1G5 T cells exposed to supernatants from seminal plasma-treated GECs.Results: Pro-inflammatory cytokines and chemokines were present at significantly higher levels in seminal plasma from acute men, whereas transforming growth factor (TGF)-beta 1 was significantly higher in seminal plasma from chronic men. Pro-inflammatory cytokine production by GECs was significantly decreased following incubation with seminal plasma from chronic men. Blocking the TGF-beta 1 receptor in GECs prior to seminal plasma exposure enhanced pro-inflammatory cytokine production. Exposure to seminal plasma activated nuclear factor (NF)-kappa B in GECs and blocking it significantly reduced pro-inflammatory cytokine production. GEC responses to seminal plasma, especially from acute men, significantly activated HIV-LTR activation in 1G5 T cells.Conclusion: Immunomodulatory factors in seminal plasma vary, depending on presence and stage of HIV infection. Exposure to seminal plasma leads to NF-kappa B activation and pro-inflammatory cytokine production, whereas TGF-beta in seminal plasma may suppress pro-inflammatory cytokine production by GECs. GEC responses to seminal plasma can activate HIV-LTR in infected CD4(+) T cells. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins