Chicken cGAS senses fowlpox virus infection and regulates macrophage effector functions
Chicken cGAS senses fowlpox virus infection and regulates macrophage effector functions
复制标题
鸡cGAS感知鸡痘病毒感染并调节巨噬细胞效应功能
DOI：
10.1101/2020.10.01.321422
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Oliveira M
中科院分区：
文献类型：
--
作者：
Oliveira M
抗病毒免疫应答依赖于受感染细胞感知外源核酸的能力。在多个物种中，模式识别受体（PRR）环状GMP-AMP合酶（cGAS）将病毒DNA感知为先天反应的重要组分。cGAS启动一系列信号传导输出，这些信号传导输出依赖于与干扰素基因的衔接蛋白刺激物（STING）结合的第二信使cGAMP的产生。在这里，我们表明，在鸡巨噬细胞中，cGAS/STING途径不仅对于响应细胞内DNA刺激产生I型干扰素是必不可少的，而且对于调节巨噬细胞效应子功能，包括MHC-II和共刺激分子的表达也是必不可少的。在鸡痘（一种禽类DNA病毒感染）的背景下，发现cGAS/STING途径负责I型干扰素产生和MHC-II转录。因此，鸡痘病毒DNA的感测对于在鸡细胞中建立抗病毒应答和调节一组特定的巨噬细胞效应子功能是必不可少的。
The anti-viral immune response is dependent on the ability of infected cells to sense foreign nucleic acids. In multiple species, the pattern recognition receptor (PRR) cyclic GMP-AMP synthase (cGAS) senses viral DNA as an essential component of the innate response. cGAS initiates a range of signaling outputs that are dependent on generation of the second messenger cGAMP that binds to the adaptor protein stimulator of interferon genes (STING). Here we show that in chicken macrophages, the cGAS/STING pathway is essential not only for the production of type-I interferons in response to intracellular DNA stimulation, but also for regulation of macrophage effector functions including the expression of MHC-II and co-stimulatory molecules. In the context of fowlpox, an avian DNA virus infection, the cGAS/STING pathway was found to be responsible for type-I interferon production and MHC-II transcription. The sensing of fowlpox virus DNA is therefore essential for mounting an anti-viral response in chicken cells and for regulation of a specific set of macrophage effector functions.