Inducible antibacterial defense system in C-elegans

Inducible antibacterial defense system in C-elegans
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DOI:
10.1016/s0960-9822(02)00928-4
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发表时间:
2002-07-23
期刊:
影响因子:
9.2
通讯作者:
Ewbank, JJ
Ewbank, JJ
中科院分区:
生物学1区
文献类型:
--
作者:
Mallo, GV;Kurz, CL;Ewbank, JJ

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先天免疫这个术语指的是一些古老的进化机制,用来保护动物和植物免受感染。遗传上易于处理的模式生物,特别是果蝇,对我们对哺乳动物先天免疫的理解做出了巨大贡献[1,2]。从本质上讲,我们对秀丽隐杆线虫的免疫反应一无所知[3,4]。利用高密度cDNA微阵列技术,研究人员发现革兰氏阴性粘质沙雷氏菌感染秀丽隐杆线虫会引起许多基因表达的显著上调。其中最强大的诱导是编码凝集素和溶菌酶的基因,已知在其他生物体中参与免疫反应。某些感染诱导基因受DBL-1/ tgf - β通路[5]的控制。我们发现dbl-1突变体对感染的易感性增加。相反,溶菌酶基因lys-1的过度表达增加了秀丽隐杆线虫对粘质葡萄球菌的抗性。这些结果首次证明了秀丽隐杆线虫具有诱导性抗菌防御,并为研究先天免疫的进化保守机制开辟了新的途径。
The term innate immunity refers to a number of evolutionary ancient mechanisms that serve to defend animals and plants against infection. Genetically tractable model organisms, especially Drosophila, have contributed greatly to advances in our understanding of mammalian innate immunity [1, 2]. Essentially, nothing is known about immune responses in the nematode Caenorhabditis elegans [3,4]. Using high-density cDNA microarrays, we show here that infection of C. elegans by the Gram-negative bacterium Serratia marcescens provokes a marked upregulation of the expression of many genes. Among the most robustly induced are genes encoding lectins and lysozymes, known to be involved in immune responses in other organisms. Certain infection-inducible genes are under the control of the DBL-1/TGFbeta pathway [5]. We found that dbl-1 mutants exhibit increased susceptibility to infection. Conversely, overexpression of the lysozyme gene lys-1 augments the resistance of C. elegrans to S. marcescens. These results constitute the first demonstration of inducible antibacterial defenses in C. elegans and open new avenues for the investigation of evolutionary conserved mechanisms of innate immunity.