TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM
TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM
复制标题
DOI：
10.1038/ni1060
复制
发表时间：
2004-05-01
影响因子：
30.5
通讯作者：
Ewbank, JJ
中科院分区：
文献类型：
--
作者：
Couillault, C;Pujol, N;Ewbank, JJ
植物和动物都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。我们在这里报告感染诱导的抗菌肽秀丽隐杆线虫的鉴定。其中两种肽（NLP-29和NLP-31）的表达受到真菌和细菌感染的差异调节，并且部分受到tir-1的控制，tir-1编码SARM（Toll-白细胞介素1受体（TIR）结构域蛋白）的直系同源物。通过RNA干扰使tir-1失活导致对感染的易感性增加。我们确定了TIR-1的蛋白质伴侣，并表明小GTTRab 1和ATP合酶的f亚基特异性地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可能代表了先前未表征但保守的先天免疫信号传导途径的组分。
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.