草履虫的肠道免疫是由病原体效应物触发的卫士蛋白 TIR-1 在溶酶体相关细胞器上的聚集激活的

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-09-18 DOI:10.1016/j.immuni.2024.08.013
Samantha Y. Tse-Kang, Khursheed A. Wani, Nicholas D. Peterson, Amanda Page, Fiachra Humphries, Read Pukkila-Worley
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引用次数: 0

摘要

具有酶活性的 Toll/白细胞介素-1/抵抗(TIR)域蛋白对植物、动物和细菌的免疫至关重要。然而,人们还不知道这些蛋白在动物的病原体感应中是如何发挥作用的。我们发现,线虫中唯一具有酶活性的TIR-domain蛋白(TIR-1,哺乳动物不育α和含TIR基团的1 [SARM1]的同源物)被战略性地表达在一个特定的细胞内区室(称为溶酶体相关细胞器)的膜上。TIR-1在溶酶体相关细胞器上的定位使线虫的肠上皮细胞能够检测病原体效应因子触发的宿主损伤。细菌病原体铜绿假单胞菌分泌的一种毒力效应物使溶酶体相关细胞器碱化和凝结。这种由病原体诱导的溶酶体相关细胞器的形态变化触发了 TIR-1 的多聚化,从而激发了其内在的 NAD+ 水解酶(NADase)活性,激活了 p38 先天免疫通路,保护宿主免受微生物感染。因此,TIR-1 是效应触发免疫反应中的一种守护蛋白,它使肠上皮细胞能够检测病原体诱发的宿主损伤。
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Intestinal immunity in C. elegans is activated by pathogen effector-triggered aggregation of the guard protein TIR-1 on lysosome-related organelles

Toll/interleukin-1/resistance (TIR)-domain proteins with enzymatic activity are essential for immunity in plants, animals, and bacteria. However, it is not known how these proteins function in pathogen sensing in animals. We discovered that the lone enzymatic TIR-domain protein in the nematode C. elegans (TIR-1, homolog of mammalian sterile alpha and TIR motif-containing 1 [SARM1]) was strategically expressed on the membranes of a specific intracellular compartment called lysosome-related organelles. The positioning of TIR-1 on lysosome-related organelles enables intestinal epithelial cells in the nematode C. elegans to survey for pathogen effector-triggered host damage. A virulence effector secreted by the bacterial pathogen Pseudomonas aeruginosa alkalinized and condensed lysosome-related organelles. This pathogen-induced morphological change in lysosome-related organelles triggered TIR-1 multimerization, which engaged its intrinsic NAD+ hydrolase (NADase) activity to activate the p38 innate immune pathway and protect the host against microbial intoxication. Thus, TIR-1 is a guard protein in an effector-triggered immune response, which enables intestinal epithelial cells to survey for pathogen-induced host damage.

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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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