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

被引:365
作者
Couillault, C
Pujol, N
Reboul, J
Sabatier, L
Guichou, JF
Kohara, Y
Ewbank, JJ
机构
[1] Univ Mediterranee, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France
[2] Inst J Paoli I Calmettes, INSERM, U119, F-13009 Marseille, France
[3] Inst Biol Mol & Cellulaire, CNRS, UPR 9022, F-67084 Strasbourg, France
[4] Univ Montpellier I, Ctr Biochim Struct, CNRS, UMR 5048,INSERM,UMR 554, F-34090 Montpellier, France
[5] Natl Inst Genet, Mishima, Shizuoka 411, Japan
基金
美国国家卫生研究院;
关键词
D O I
10.1038/ni1060
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:488 / 494
页数:7
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