HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon production, maturation, and migration

HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon production, maturation, and migration
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DOI:
10.1016/j.virol.2005.09.059
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发表时间:
2005-12-20
期刊:
影响因子:
3.7
通讯作者:
Levy, JA
Levy, JA
中科院分区:
医学3区
文献类型:
--
作者:
Schmidt, B;Ashlock, BM;Levy, JA

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浆细胞样树突状细胞(Plasmacytoid dendritic cells,PDC)是天然的1型干扰素(type-1 interferon,IFN)产生细胞,在天然抗HIV免疫应答中发挥作用。以前的报道表明PDC IFN的产生是由HIV诱导的。我们的研究结果表明,一个更强大的IFN诱导时,纯化的PDC(95%)暴露于HIV感染的细胞。在非活细胞、从感染细胞提取的DNA和RNA以及病毒蛋白质中未观察到这种效应。该反应被抗CD 4和中和抗gp 120抗体以及可溶性CD 4阻断。HIV感染细胞的IFN诱导也被低剂量的氯喹阻止,氯喹抑制内体酸化。PDC IFN释放导致感染的CD 4+细胞的HIV产生减少,支持PDC的抗HIV活性。刺激的CD 4+细胞诱导PDC活化和成熟;仅HIV感染的CD 4+细胞增强PDC迁移标记物(CCR 7)。后一项发现可以解释HIV感染者中循环PDC的下降。(c)2005年爱思唯尔公司All rights reserved.
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-gp 120 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. (c) 2005 Elsevier Inc. All rights reserved.