IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism
IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism
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DOI：
10.4049/jimmunol.173.12.7416
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发表时间：
2004-12-15
影响因子：
4.4
通讯作者：
Decker, T
中科院分区：
文献类型：
--
作者：
Stockinger, S;Reutterer, B;Decker, T
像病毒一样，细胞内细菌刺激其宿主细胞产生I型ifn （ifn - α和ifn - β）。在我们的研究中，我们研究了与和的合成有关的信号和分子。单核增生李斯特菌感染小鼠巨噬细胞对干扰素的反应。我们报告说，IFN- β是感染期间产生的关键的即时早期IFN，因为所有其他I型IFN的合成，感染诱导基因子集的表达，以及对I型IFN的生物反应在IFN- β缺乏时丢失。IFN- β mRNA的诱导和巨噬细胞对细菌诱导死亡的IFN- β依赖性敏化，反过来完全依赖于转录因子IFN调节因子3 （IRF3）的存在。ifn - β合成和信号转导发生在TLR或其接头MyD88、TRIF或TRAM缺失的巨噬细胞中。细胞内细菌的候选受体Nod2的表达在感染期间增加，但该蛋白不是李斯特菌诱导的ifn - β基因信号转导所必需的。基于我们的数据，我们提出IRF3是来自结构不相关的细胞内病原体的信号的汇聚点，并且单核增生L. L.刺激新的TLR-和nod2独立通路来靶向IRF3和I型IFN基因。
Like viruses, intracellular bacteria stimulate their host cells to produce type I IFNs (IFN-alpha and IFN-beta). In our study, we investigated the signals and molecules relevant for the synthesis of and. response to IFN by mouse macrophages infected with Listeria monocytogenes. We report that IFN-beta is the critical immediate-early IFN made during infection, because the synthesis of all other type I IFN, expression of a subset of infection-induced genes, and the biological response to type I IFN was lost upon IFN-beta deficiency. The induction of IFN-beta mRNA and the IFN-beta-dependent sensitization of macrophages to bacteria-induced death, in turn, was absolutely dependent upon the presence of the transcription factor IFN regulatory factor 3 (IRF3). IFN-beta synthesis and signal transduction occurred in macrophages deficient for TLR or their adaptors MyD88, TRIF, or TRAM. Expression of Nod2, a candidate receptor for intracellular bacteria, increased during infection, but the protein was not required for Listeria-induced signal transduction to the Ifn-beta gene. Based on our data, we propose that IRF3 is a convergence point for signals derived from structurally unrelated intracellular pathogens, and that L. monocytogenes stimulates a novel TLR- and Nod2-independent pathway to target IRF3 and the type I IFN genes.