Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans

Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans
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DOI:
10.1128/iai.00034-19
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发表时间:
2019-04-01
影响因子:
3.1
通讯作者:
McMullan, Rachel
McMullan, Rachel
中科院分区:
医学2区
文献类型:
--
作者:
Anderson, Alexandra;Chew, Yee Lian;McMullan, Rachel

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G蛋白偶联受体参与动物界的宿主防御,转导许多涉及脊椎动物和无脊椎动物免疫反应的信号。虽然已经确定线虫秀丽隐杆线虫在感染许多细菌、真菌和病毒病原体后触发先天性免疫应答,但秀丽隐杆线虫的机制还不清楚。秀丽线虫认识到这些病原体仍然有些难以捉摸。C.线虫G蛋白偶联受体与识别病原体相关损伤和激活下游宿主免疫应答有关。在这里,我们确定和表征一种新的G蛋白偶联受体所需的调节C。线虫对嗜热微杆菌感染的反应。我们表明,这种受体,我们指定的病原体清除缺陷型受体1(PCDR-1),需要有效的病原体清除感染后。PCDR-1作用于多种G蛋白的上游,包括C. elegans G alpha q直系同源物EGL-30在直肠上皮细胞中通过新机制促进病原体清除。
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 Caenorhabditis elegans triggers innate immune responses following infection with numerous bacterial, fungal, and viral pathogens, the mechanisms by which C. elegans recognizes these pathogens have remained somewhat more elusive. C. elegans 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 C. elegans response to infection with Microbacterium nematophilum. 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 C. elegans G alpha q ortholog, EGL-30, in rectal epithelial cells to promote pathogen clearance via a novel mechanism.