Schmidt Barbara, Ashlock Brittany M, Foster Hillary, Fujimura Sue H, Levy Jay A
Department of Medicine, Division Hematology/Oncology, University of California, San Francisco, CA 94143-0128, USA.
Virology. 2005 Dec 20;343(2):256-66. doi: 10.1016/j.virol.2005.09.059. Epub 2005 Nov 8.
Plasmacytoid dendritic cells (PDC), natural type-1 interferon (IFN) producing cells, could play a role in the innate anti-HIV immune response. Previous reports indicated that PDC IFN production is induced by HIV. Our results show a more robust IFN induction when purified PDC (>95%) were exposed to HIV-infected cells. This effect was not observed with non-viable cells, DNA, and RNA extracted from infected cells, and viral proteins. The response was blocked by anti-CD4 and neutralizing anti-gp120 antibodies as well as soluble CD4. IFN induction by HIV-infected cells was also prevented by low-dose chloroquine, which inhibits endosomal acidification. PDC IFN release resulted in reduced HIV production by infected CD4+ cells, supporting an anti-HIV activity of PDC. Stimulated CD4+ cells induced PDC activation and maturation; markers for PDC migration (CCR7) were enhanced by HIV-infected CD4+ cells only. This latter finding could explain the decline in circulating PDC in HIV-infected individuals.
浆细胞样树突状细胞(pDC)是产生天然I型干扰素(IFN)的细胞,可能在先天性抗HIV免疫反应中发挥作用。先前的报道表明,HIV可诱导pDC产生IFN。我们的结果显示,当纯化的pDC(>95%)暴露于HIV感染的细胞时,会诱导出更强的IFN。用从感染细胞中提取的无活性细胞、DNA、RNA以及病毒蛋白处理时,未观察到这种效应。抗CD4和中和抗gp120抗体以及可溶性CD4可阻断该反应。低剂量氯喹可抑制内体酸化,也能阻止HIV感染细胞诱导IFN。pDC释放IFN可使感染的CD4+细胞的HIV产生减少,这支持了pDC的抗HIV活性。受刺激的CD4+细胞可诱导pDC活化和成熟;仅HIV感染的CD4+细胞可增强pDC迁移标志物(CCR7)。后一发现可以解释HIV感染者循环pDC数量的下降。
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