Department of Life Sciences, Imperial College London, London, United Kingdom.
Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Infect Immun. 2019 Mar 25;87(4). doi: 10.1128/IAI.00034-19. Print 2019 Apr.
G protein-coupled receptors contribute to host defense across the animal kingdom, transducing many signals involved in both vertebrate and invertebrate immune responses. While it has become well established that the nematode worm triggers innate immune responses following infection with numerous bacterial, fungal, and viral pathogens, the mechanisms by which recognizes these pathogens have remained somewhat more elusive. G protein-coupled receptors have been implicated in recognizing pathogen-associated damage and activating downstream host immune responses. Here we identify and characterize a novel G protein-coupled receptor required to regulate the response to infection with We show that this receptor, which we designate pathogen clearance-defective receptor 1 (PCDR-1), is required for efficient pathogen clearance following infection. PCDR-1 acts upstream of multiple G proteins, including the Gαq ortholog, EGL-30, in rectal epithelial cells to promote pathogen clearance via a novel mechanism.
G 蛋白偶联受体在动物界中有助于宿主防御,转导参与脊椎动物和无脊椎动物免疫反应的许多信号。虽然线虫蠕虫 在感染多种细菌、真菌和病毒病原体后会引发先天免疫反应已经得到充分证实,但线虫蠕虫 识别这些病原体的机制仍然有些难以捉摸。G 蛋白偶联受体已被牵连到识别与病原体相关的损伤并激活下游宿主免疫反应。在这里,我们鉴定并描述了一个新型 G 蛋白偶联受体,该受体需要调节 对线虫蠕虫 的感染反应。我们表明,该受体(我们指定为病原体清除缺陷受体 1(PCDR-1))在感染后清除病原体是必需的。PCDR-1 在直肠上皮细胞中作用于多个 G 蛋白(包括 Gαq 同源物 EGL-30)的上游,通过一种新的机制促进病原体清除。