C. elegans detects pathogen-induced translational inhibition to activate immune signaling

Cell Host Microbe. 2012 Apr 19;11(4):375-86. doi: 10.1016/j.chom.2012.02.008.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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


  • Bacterial Toxins
  • Caenorhabditis elegans Proteins
  • Exotoxins
  • Transcription Factors
  • Virulence Factors
  • ADP Ribose Transferases
  • Pseudomonas aeruginosa exotoxin A