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

被引：17

作者：

Peterson, Nicholas D. ^{[1
]}

Tse, Samantha Y. ^{[1
]}

Huang, Qiuyu Judy ^{[2
]}

Wani, Khursheed A. ^{[1
]}

Schiffer, Celia A. ^{[2
]}

Pukkila-Worley, Read ^{[1
]}

机构：

[1] Univ Massachusetts, Dept Med, Program Innate Immun, Div Infect Dis & Immunol,Chan Med Sch, Worcester, MA 01655 USA

[2] Univ Massachusetts, Dept Biochem & Mol Biotechnol, Chan Med Sch, Worcester, MA USA

来源：

IMMUNITY | 2023年 / 56卷 / 04期

关键词：

CAENORHABDITIS-ELEGANS; IMMUNE-RESPONSE; TRANSCRIPTION FACTOR; FUNCTIONAL-ANALYSIS; TRANSLATIONAL INHIBITION; GENETIC INTERFERENCE; MITOCHONDRIAL UPR; INNATE IMMUNITY; FORCE-FIELD; PSEUDOMONAS;

D O I：

10.1016/j.immuni.2023.01.027

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Distinguishing infectious pathogens from harmless microorganisms is essential for animal health. The mech-anisms 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 Caeno-rhabditis 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.

引用

页码：768 / +

页数：25