Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum
Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum
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DOI：
10.1101/gr.50823006
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发表时间：
2006-08-01
期刊：
影响因子：
7
通讯作者：
Hodgkin, Jonathan
中科院分区：
文献类型：
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作者：
O'Rourke, Delia;Baban, Dilair;Hodgkin, Jonathan
线虫秀丽隐杆线虫和革兰氏阳性细菌病原体嗜热微杆菌之间的相互作用为线虫中的先天免疫应答提供了模型。这种病原体附着于蠕虫的直肠和肛门后表皮，导致生长缓慢、便秘和直肠下皮细胞的防御性肿胀反应。为了探索病原体攻击后蠕虫激活的基因组反应，我们使用微阵列分析6小时感染后诱导的转录变化，比较毒力与无毒力感染。我们定义了89个基因，其中68个基因表达上调，21个基因表达下调。在前者中，那些编码C型凝集素结构域是最丰富的类。89个基因中的许多基因表现出基因组聚类，我们确定了一个由62个基因组成的大簇，其中大多数基因是在对感染的反应中诱导的。我们使用突变体或RNAi测试了41个参与免疫的诱导基因，发现其中6个是肿胀反应所需的，5个是防御所需的。我们的研究结果表明，C型凝集素和其他假定的病原体识别分子是重要的先天性免疫防御在C。优雅的。我们还发现了编码溶菌酶、蛋白酶和防御相关蛋白以及各种未知功能域的基因的显著诱导。这些基因在感染M.嗜热假单胞菌与其他病原菌诱导的基因有很大区别，表明嗜热假单胞菌是一种重要的致病菌。线虫对感染产生病原体特异性反应。
The interaction between the nematode Caenorhabditis elegans and a Gram-positive bacterial pathogen, Microbacterium nematophilum, provides a model for an innate immune response in nematodes. This pathogen adheres to the rectal and post-anal cuticle of the worm, causing slowed growth, constipation, and a defensive swelling response of rectal hypodermal cells. To explore the genomic responses that the worm activates after pathogenic attack we used microarray analysis of transcriptional changes induced after 6-h infection, comparing virulent with avirulent infection. We defined 89 genes with statistically significant expression changes of at least twofold, of which 68 were up-regulated and 21 were down-regulated. Among the former, those encoding C-type lectin domains were the most abundant class. Many of the 89 genes exhibit genomic clustering, and we identified one large cluster of 62 genes, of which most were induced in response to infection. We tested 41 of the induced genes for involvement in immunity using mutants or RNAi, finding that six of these are required for the swelling response and five are required more generally for defense. Our results indicate that C-type lectins and other putative pathogen- recognition molecules are important for innate immune defense in C. elegans. We also found significant induction of genes encoding lysozymes, proteases, and defense-related proteins, as well as various domains of unknown function. The genes induced during infection by M. nematophilum appear largely distinct from genes induced by other pathogens, suggesting that C. elegans mounts pathogen- specific responses to infection.