美国马萨诸塞大学陈医学院Read Pukkila-Worley团队近期取得重要工作进展，他们研究发现秀丽隐杆线虫可以通过核激素受体对病原体来源代谢物的非典型识别模式来区分饮食中的毒性细菌。相关研究成果2023年2月17日在线发表于《免疫》杂志上。

据介绍，区分传染性病原体和无害微生物对动物健康至关重要。用于识别感染性微生物的机制尚未完全了解，特别是在以细菌为食物来源的后生动物宿主中。

研究人员描述了秀丽隐杆线虫（C.elegans）中的一个非典型模式识别系统，该系统评估了强毒铜绿假单胞菌（P.aeruginosa）激活先天免疫的相对威胁。研究人员发现C.elegans的先天免疫反应是由吩嗪-1-甲酰胺（PCN）触发的，这是一种由铜绿假单胞菌致病菌株产生的有毒代谢产物。研究人员鉴定了核激素受体NHR-86/HNF4作为C.elegans中的PCN传感器，并验证了PCN与NHR-86/NNF4的配体结合域结合。PCN对NHR-86/HNF4的激活直接参与了肠上皮细胞中的一个转录程序，该转录程序保护了对铜绿假单胞菌的抵抗。

因此，细菌代谢产物是线虫监测的一种致病模式，以识别其细菌饮食中的病原体。

附：英文原文

Title: Non-canonical pattern recognition of a pathogen-derived metabolite by a nuclear hormone receptor identifies virulent bacteria in C. elegans

Author: Nicholas D. Peterson, Samantha Y. Tse, Qiuyu Judy Huang, Khursheed A. Wani, Celia A. Schiffer, Read Pukkila-Worley

Issue&Volume: 2023-02-17

Abstract: Distinguishing infectious pathogens from harmless microorganisms is essential for animal health. The mechanisms used to identify infectious microbes are not fully understood, particularly in metazoan hosts that eat bacteria as their food source. Here, we characterized a non-canonical pattern-recognition system in Caenorhabditis elegans (C. elegans) that assesses the relative threat of virulent Pseudomonas aeruginosa (P. Aeruginosa) to activate innate immunity. We discovered that the innate immune response in C. elegans was triggered by phenazine-1-carboxamide (PCN), a toxic metabolite produced by pathogenic strains of P. aeruginosa. We identified the nuclear hormone receptor NHR-86/HNF4 as the PCN sensor in C. elegans and validated that PCN bound to the ligand-binding domain of NHR-86/HNF4. Activation of NHR-86/HNF4 by PCN directly engaged a transcriptional program in intestinal epithelial cells that protected against P. aeruginosa. Thus, a bacterial metabolite is a pattern of pathogenesis surveilled by nematodes to identify a pathogen in its bacterial diet.

DOI: 10.1016/j.immuni.2023.01.027

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00039-0