Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells.
Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells.
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DOI：
10.1084/jem.20030162
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发表时间：
2003-08-04
期刊：
影响因子：
--
通讯作者：
Iwasaki A
中科院分区：
文献类型：
--
作者：
Lund J;Sato A;Akira S;Medzhitov R;Iwasaki A
浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDC）是一类能分泌I型干扰素（interferon，IFN）的细胞。在这项研究中，我们研究了pDC识别病毒的分子机制。首先，我们证明了来自小鼠骨髓的CD 11 c +Gr-1 intB 220 + pDC在对活的或UV灭活的单纯疱疹病毒-2（HSV-2）的应答中分泌高水平的IFN-α。接下来，我们确定pDC分泌IFN-α需要衔接分子MyD 88的表达，这表明Toll样受体（TLR）参与HSV-2识别。为了测试TLR是否介导HSV-2诱导的IFN-α从pDC分泌，检查了各种敲除小鼠。这些实验揭示了在这个过程中对TLR 9的明确需求。此外，我们证明了纯化的HSV-2 DNA可以触发pDC分泌IFN-α，并且抑制性CpG寡核苷酸处理以剂量依赖性方式减少HSV诱导的pDC分泌IFN-α。TLR 9对HSV-2的识别是通过内吞途径介导的，该途径被氯喹或巴弗洛霉素A1抑制。通过体内接种HSV-2进一步证实了IFN-α分泌对TLR 9的严格要求。因此，这些结果证明了一种新的机制，其中病毒的基因组DNA可以接合TLR 9并导致pDC分泌IFN-α。
Plasmacytoid dendritic cells (pDCs) have been identified as a potent secretor of the type I interferons (IFNs) in response to CpG as well as several viruses. In this study, we examined the molecular mechanism of virus recognition by pDCs. First, we demonstrated that the CD11c+Gr-1intB220+ pDCs from mouse bone marrow secreted high levels of IFN-α in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-α secretion by pDCs required the expression of the adaptor molecule MyD88, suggesting the involvement of a Toll-like receptor (TLR) in HSV-2 recognition. To test whether a TLR mediates HSV-2–induced IFN-α secretion from pDCs, various knockout mice were examined. These experiments revealed a clear requirement for TLR9 in this process. Further, we demonstrated that purified HSV-2 DNA can trigger IFN-α secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-α secretion by pDCs in a dose-dependent manner. The recognition of HSV-2 by TLR9 was mediated through an endocytic pathway that was inhibited by chloroquine or bafilomycin A1. The strict requirement for TLR9 in IFN-α secretion was further confirmed by the inoculation of HSV-2 in vivo. Therefore, these results demonstrate a novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-α by pDCs.
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DOI：
10.1084/jem.20020045
发表时间：
2002-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gilliet M;Boonstra A;Paturel C;Antonenko S;Xu XL;Trinchieri G;O'Garra A;Liu YJ
通讯作者：
Liu YJ
影响因子：
56.9
作者：
MULLER, U;STEINHOFF, U;AGUET, M
通讯作者：
AGUET, M
影响因子：
4.4
作者：
Brawand, P;Fitzpatrick, DR;De Smedt, T
通讯作者：
De Smedt, T
影响因子：
4.4
作者：
Hornung, V;Rothenfusser, S;Hartmann, G
通讯作者：
Hartmann, G
影响因子：
3.7
作者：
Jones, CA;Taylor, TJ;Knipe, DM
通讯作者：
Knipe, DM