Yonsei Proteome Research Center Department of Biochemistry and Integrated Omics for Biomedical Science, College of Life Science and Biotechnology, World Class University Program, Graduate School, Yonsei University, Seoul, Korea.
Aging Cell. 2011 Apr;10(2):208-19. doi: 10.1111/j.1474-9726.2010.00655.x. Epub 2011 Feb 21.
Innate immune responses to pathogens are governed by the nervous system. Here, we investigated the molecular mechanism underlying innate immunity in Caenorhabditis elegans against Escherichia coli OP50, a standard laboratory C. elegans food. Longevity was compared in worms fed live or UV-killed OP50 at low or high density food condition (HDF). Expression of the antimicrobial gene lys-8 was approximately 5-fold higher in worms fed live OP50, suggesting activation of innate immunity upon recognition of OP50 metabolites. Lifespan was extended and SOD-3 mRNA levels were increased in gpa-9-overexpressing gpa-9XS worms under HDF in association with robust induction of insulin/IGF-1 signaling (IIS). Expression of ins-7 and daf-28 that control lys-8 expression was reduced in gpa-9XS, indicating that GPA-9-mediated immunity is due in part to ins-7 and daf-28 downregulation. Our results suggest that OP50 metabolites in amphid neurons elicit innate immunity through the IIS pathway, and identify GPA-9 as a novel regulator of both the immune system and aging in C. elegans.
先天免疫反应受神经系统调控。在这里，我们研究了秀丽隐杆线虫（Caenorhabditis elegans）针对大肠杆菌 OP50（一种标准的实验室用秀丽隐杆线虫食物）的先天免疫的分子机制。在低密度（LD）或高密度（HD）食物条件下，比较了喂食活的或紫外线杀死的 OP50 的线虫的寿命。喂食活 OP50 的线虫中抗菌基因 lys-8 的表达水平升高了约 5 倍，表明在识别 OP50 代谢物后激活了先天免疫。在与胰岛素/IGF-1 信号（IIS）强烈诱导相关的情况下，在高密度食物条件下，过度表达 gpa-9 的 gpa-9XS 线虫的寿命延长，SOD-3 mRNA 水平升高。gpa-9XS 中 ins-7 和 daf-28 的表达（控制 lys-8 的表达）降低，表明 GPA-9 介导的免疫部分归因于 ins-7 和 daf-28 的下调。我们的研究结果表明，在感觉神经元中的 OP50 代谢物通过 IIS 途径引发先天免疫，并鉴定出 GPA-9 是秀丽隐杆线虫免疫系统和衰老的新型调节剂。
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