Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection.
Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection.
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I 型干扰素表达和对急性 DNA 病毒感染的抵抗所需的两种病原体感应途径的顺序激活。
DOI：
10.1016/j.immuni.2015.11.015
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发表时间：
2015-12-15
期刊：
影响因子：
32.4
通讯作者：
Sigal LJ
中科院分区：
文献类型：
--
作者：
Xu RH;Wong EB;Rubio D;Roscoe F;Ma X;Nair S;Remakus S;Schwendener R;John S;Shlomchik M;Sigal LJ
Toll样受体9（TLR 9）、其接头MyD 88、下游转录因子干扰素调节因子7（IRF 7）和I型干扰素（IFN-I）都是抵抗鼠痘病毒（ECTV）感染所必需的。然而，目前还不知道这些效应器如何或在哪些细胞中起作用以促进存活。在这里，我们发现，感染ECTV后，TLR 9-MyD 88-IRF 7通路是CD 11 c+细胞表达促炎性细胞因子和向引流淋巴结（D-LN）募集炎性单核细胞（iMo）所必需的。在D-LN中，IFN-I的主要产生者被感染iMo，iMo利用DNA传感器-适配器STING激活IRF 7和核因子κB（NF-κB）信号，分别诱导IFNα和IFNβ的表达。因此，在体内，DNA病原体传感的两个途径在两种不同的细胞类型中顺序地起作用，以协调对病毒疾病的抗性。
Toll Like Receptor 9 (TLR9), its adapter MyD88, the downstream transcription factor interferon regulatory factor 7 (IRF7) and type I interferons (IFN-I) are all required for resistance to infection with ectromelia virus (ECTV). However, it is not known how or in which cells these effectors function to promote survival. Here, we showed that after infection with ECTV, the TLR9-MyD88-IRF7 pathway was necessary in CD11c+ cells for the expression of proinflammatory cytokines and the recruitment of inflammatory monocytes (iMo) to the draining lymph node (D-LN). In the D-LN, the major producers of IFN-I were infected iMo, which used the DNA sensor-adapter STING to activate IRF7 and nuclear factor κB (NF-κB) signaling to induce the expression of IFNα and IFNβ, respectively. Thus, in vivo, two pathways of DNA pathogen sensing act sequentially in two distinct cell types to orchestrate resistance to a viral disease.