RRC ID 46327
Author Dunbar TL, Yan Z, Balla KM, Smelkinson MG, Troemel ER.
Title C. elegans detects pathogen-induced translational inhibition to activate immune signaling.
Journal Cell Host Microbe
Abstract Pathogens commonly disrupt host cell processes or cause damage, but the surveillance mechanisms used by animals to monitor these attacks are poorly understood. Upon infection with pathogenic Pseudomonas aeruginosa, the nematode C. elegans upregulates infection response gene irg-1 using the zip-2 bZIP transcription factor. Here we show that P. aeruginosa infection inhibits mRNA translation in the intestine via the endocytosed translation inhibitor Exotoxin A, which leads to an increase in ZIP-2 protein levels. In the absence of infection we find that the zip-2/irg-1 pathway is upregulated following disruption of several core host processes, including inhibition of mRNA translation. ZIP-2 induction is conferred by a conserved upstream open reading frame in zip-2 that could derepress ZIP-2 translation upon infection. Thus, translational inhibition, a common pathogenic strategy, can trigger activation of an immune surveillance pathway to provide host defense.
Volume 11(4)
Pages 375-86
Published 2012-4-19
DOI 10.1016/j.chom.2012.02.008
PII S1931-3128(12)00092-3
PMID 22520465
PMC PMC3334869
MeSH ADP Ribose Transferases / genetics ADP Ribose Transferases / immunology Animals Bacterial Toxins / genetics Bacterial Toxins / immunology Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / immunology Down-Regulation Exotoxins / genetics Exotoxins / immunology Host-Pathogen Interactions* Humans Immunity, Innate Protein Biosynthesis* Pseudomonas Infections / genetics Pseudomonas Infections / immunology* Pseudomonas Infections / microbiology Pseudomonas aeruginosa / genetics Pseudomonas aeruginosa / immunology* Pseudomonas aeruginosa / physiology Signal Transduction Transcription Factors / genetics Transcription Factors / immunology Virulence Factors / genetics Virulence Factors / immunology
IF 15.923
Times Cited 109
C.elegans tm4067 tm4248