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秀丽隐杆线虫中由TIR结构域衔接蛋白TIR-1(人类SARM的直系同源物)对先天免疫进行的不依赖Toll样受体(TLR)的调控

TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM.

作者信息

Couillault Carole, Pujol Nathalie, Reboul Jérôme, Sabatier Laurence, Guichou Jean-François, Kohara Yuji, Ewbank Jonathan J

机构信息

Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.

出版信息

Nat Immunol. 2004 May;5(5):488-94. doi: 10.1038/ni1060. Epub 2004 Mar 28.

DOI:10.1038/ni1060
PMID:15048112
Abstract

Both plants and animals respond to infection by synthesizing compounds that directly inhibit or kill invading pathogens. We report here the identification of infection-inducible antimicrobial peptides in Caenorhabditis elegans. Expression of two of these peptides, NLP-29 and NLP-31, was differentially regulated by fungal and bacterial infection and was controlled in part by tir-1, which encodes an ortholog of SARM, a Toll-interleukin 1 receptor (TIR) domain protein. Inactivation of tir-1 by RNA interference caused increased susceptibility to infection. We identify protein partners for TIR-1 and show that the small GTPase Rab1 and the f subunit of ATP synthase participate specifically in the control of antimicrobial peptide gene expression. As the activity of tir-1 was independent of the single nematode Toll-like receptor, TIR-1 may represent a component of a previously uncharacterized, but conserved, innate immune signaling pathway.

摘要

植物和动物都会通过合成直接抑制或杀死入侵病原体的化合物来应对感染。我们在此报告在秀丽隐杆线虫中鉴定出感染诱导型抗菌肽。其中两种肽NLP-29和NLP-31的表达受真菌和细菌感染的差异调节,并且部分受tir-1控制,tir-1编码SARM的直系同源物,SARM是一种Toll样白细胞介素1受体(TIR)结构域蛋白。通过RNA干扰使tir-1失活会导致对感染的易感性增加。我们鉴定了TIR-1的蛋白质伴侣,并表明小GTP酶Rab1和ATP合酶的f亚基特别参与抗菌肽基因表达的控制。由于tir-1的活性独立于单个线虫Toll样受体,TIR-1可能代表了一个以前未被表征但保守的固有免疫信号通路的组成部分。

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