Baculovirus Induces Type I Interferon Production through Toll-Like Receptor-Dependent and -Independent Pathways in a Cell-Type-Specific Manner
Baculovirus Induces Type I Interferon Production through Toll-Like Receptor-Dependent and -Independent Pathways in a Cell-Type-Specific Manner
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DOI：
10.1128/jvi.00679-09
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发表时间：
2009-08-01
影响因子：
5.4
通讯作者：
Matsuura, Yoshiharu
中科院分区：
文献类型：
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作者：
Abe, Takayuki;Kaname, Yuuki;Matsuura, Yoshiharu
加州签名虫核型多角体病毒（AcNPV）是一种对昆虫致病的双链dna病毒。研究表明，AcNPV在哺乳动物免疫细胞中诱导先天免疫反应，并赋予小鼠免受致命病毒感染的保护。在这项研究中，我们发现AcNPV在小鼠浆细胞样树突状细胞（pDCs）和非pDCs（如腹膜巨噬细胞和脾CD11c(+) dc）中分别通过toll样受体（TLR）依赖性和非依赖性途径介导I型干扰素（IFN）的产生。IFN调节因子7 （IRF7）不仅在体外而且在体内均在免疫细胞AcNPV产生I型IFN中发挥关键作用。在小鼠胚胎成纤维细胞（MEFs）中，AcNPV通过tlr依赖性和IRF3依赖性途径产生ifn - β和ifn诱导的趋化因子，而不是通过tlr依赖性和IRF3/ irf7依赖性产生促炎细胞因子。尽管在水疱性口炎病毒感染后，IFN启动子刺激因子1 （IPS-1）缺陷mef中IFN- β和IFN诱导的趋化因子的产生严重受损，但AcNPV在IPS-1缺陷mef中产生了大量的细胞因子。这些结果表明，在AcNPV感染反应中，除了TLR-和ips -1依赖的信号通路外，还有一种新的信号通路参与了I型IFN的产生。
Autographa californica nuclear polyhedrosis virus (AcNPV) is a double-stranded-DNA virus that is pathogenic to insects. AcNPV was shown to induce an innate immune response in mammalian immune cells and to confer protection of mice from lethal viral infection. In this study, we have shown that production of type I interferon (IFN) by AcNPV in murine plasmacytoid dendritic cells (pDCs) and non-pDCs, such as peritoneal macrophages and splenic CD11c(+) DCs, was mediated by Toll-like receptor (TLR)-dependent and -independent pathways, respectively. IFN regulatory factor 7 (IRF7) was shown to play a crucial role in the production of type I IFN by AcNPV not only in immune cells in vitro but also in vivo. In mouse embryonic fibroblasts (MEFs), AcNPV produced IFN-beta and IFN-inducible chemokines through TLR-independent and IRF3-dependent pathways, in contrast to the TLR-dependent and IRF3/IRF7-independent production of proinflammatory cytokines. Although production of IFN-beta and IFN-inducible chemokines was severely impaired in IFN promoter-stimulator 1 (IPS-1)-deficient MEFs upon infection with vesicular stomatitis virus, AcNPV produced substantial amounts of the cytokines in IPS-1-deficient MEFs. These results suggest that a novel signaling pathway(s) other than TLR- and IPS-1-dependent pathways participates in the production of type I IFN in response to AcNPV infection.