果蝇 STING 分析揭示了一种进化保守的抗菌功能。
Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function.
机构信息
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA; Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
出版信息
Cell Rep. 2018 Jun 19;23(12):3537-3550.e6. doi: 10.1016/j.celrep.2018.05.029.
The vertebrate protein STING, an intracellular sensor of cyclic dinucleotides, is critical to the innate immune response and the induction of type I interferon during pathogenic infection. Here, we show that a STING ortholog (dmSTING) exists in Drosophila, which, similar to vertebrate STING, associates with cyclic dinucleotides to initiate an innate immune response. Following infection with Listeria monocytogenes, dmSTING activates an innate immune response via activation of the NF-κB transcription factor Relish, part of the immune deficiency (IMD) pathway. DmSTING-mediated activation of the immune response reduces the levels of Listeria-induced lethality and bacterial load in the host. Of significance, dmSTING triggers an innate immune response in the absence of a known functional cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) ortholog in the fly. Together, our results demonstrate that STING is an evolutionarily conserved antimicrobial effector between flies and mammals, and it comprises a key component of host defense against pathogenic infection in Drosophila.
脊椎动物蛋白 STING 是细胞内环二核苷酸的细胞内传感器，对先天免疫反应和致病性感染期间 I 型干扰素的诱导至关重要。在这里，我们表明果蝇中存在 STING 同源物（dmSTING），类似于脊椎动物 STING，与环二核苷酸结合以引发先天免疫反应。在感染李斯特菌后，dmSTING 通过激活免疫缺陷（IMD）途径的转录因子 Relish 激活先天免疫反应。dmSTING 介导的免疫反应的激活降低了宿主中李斯特菌诱导的致死率和细菌载量。重要的是，dmSTING 在果蝇中缺乏已知的功能性环鸟苷酸单磷酸（GMP）-AMP 合酶（cGAS）同源物的情况下触发先天免疫反应。总之，我们的结果表明 STING 是果蝇和哺乳动物之间进化保守的抗菌效应物，它是宿主防御致病性感染的关键组成部分。
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