Non-canonical Pattern Recognition of a Pathogen-derived Metabolite by a Nuclear Hormone Receptor Identifies Virulent Bacteria in C. elegans

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2023 Feb 22

PMID 36804958

Authors

Nicholas D Peterson

Samantha Y Tse

Qiuyu Judy Huang

Khursheed A Wani

Celia A Schiffer

Read Pukkila-Worley

Affiliations

Soon will be listed here.

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.

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