美国麻省大学Read Pukkila-Worley研究组发现，秀丽隐杆线虫中的肠道免疫通过病原效应蛋白触发的，守卫蛋白TIR-1在溶酶体相关细胞器上的聚集被激活。相关论文于2024年9月18日在线发表于国际学术期刊《免疫》。

研究人员发现，线虫秀丽隐杆线虫中的唯一酶活性Toll/白介素-1/抗性（TIR）结构域蛋白TIR-1（哺乳动物无菌α和TIR基序含有1 [SARM1] 的同源物），被战略性地表达在一种特定的细胞内区室——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监测由病原效应蛋白触发的宿主损伤。

细菌病原体铜绿假单胞菌分泌的毒力效应蛋白，使溶酶体相关细胞器碱化并凝聚。这种由病原体诱导的溶酶体相关细胞器形态变化，引发了TIR-1的多聚化，激活其内在的NAD⁺水解酶（NADase）活性，进而启动p38先天免疫通路，保护宿主免受微生物毒害。因此，TIR-1是效应蛋白触发的免疫反应中的守卫蛋白，使肠上皮细胞能够监测病原体引发的宿主损伤。

据了解，具有酶活性TIR结构域蛋白在植物、动物和细菌的免疫系统中至关重要。然而，这些蛋白质在动物中如何感知病原体尚不清楚。

附：英文原文

Title: Intestinal immunity in C. elegans is activated by pathogen effector-triggered aggregation of the guard protein TIR-1 on lysosome-related organelles

Author: Samantha Y. Tse-Kang, Khursheed A. Wani, Nicholas D. Peterson, Amanda Page, Fiachra Humphries, Read Pukkila-Worley

Issue&Volume: 2024-09-18

Abstract: 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.

DOI: 10.1016/j.immuni.2024.08.013

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00412-6