RRC ID 46404
Author McEwan DL, Kirienko NV, Ausubel FM.
Title Host translational inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an immune response in Caenorhabditis elegans.
Journal Cell Host Microbe
Abstract Intestinal epithelial cells are exposed to both innocuous and pathogenic microbes, which need to be distinguished to mount an effective immune response. To understand the mechanisms underlying pathogen recognition, we investigated how Pseudomonas aeruginosa triggers intestinal innate immunity in Caenorhabditis elegans, a process independent of Toll-like pattern recognition receptors. We show that the P. aeruginosa translational inhibitor Exotoxin A (ToxA), which ribosylates elongation factor 2 (EF2), upregulates a significant subset of genes normally induced by P. aeruginosa. Moreover, immune pathways involving the ATF-7 and ZIP-2 transcription factors, which protect C. elegans from P. aeruginosa, are required for preventing ToxA-mediated lethality. ToxA-responsive genes are not induced by enzymatically inactive ToxA protein but can be upregulated independently of ToxA by disruption of host protein translation. Thus, C. elegans has a surveillance mechanism to recognize ToxA through its effect on protein translation rather than by direct recognition of either ToxA or ribosylated EF2.
Volume 11(4)
Pages 364-74
Published 2012-4-19
DOI 10.1016/j.chom.2012.02.007
PII S1931-3128(12)00091-1
PMID 22520464
PMC PMC3334877
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 Virulence Factors / genetics Virulence Factors / immunology*
IF 15.923
Times Cited 102
C.elegans tm4248 tm4067