title: C. elegans detects pathogen-induced translational inhibition to activate immune signaling.
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.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Dunbar
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yan
authors.forename: Keir M
authors.initials: KM
authors.lastname: Balla
authors.forename: Margery G
authors.initials: MG
authors.lastname: Smelkinson
authors.forename: Emily R
authors.initials: ER
authors.lastname: Troemel
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000276:immunology; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation; D005098:Exotoxins / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D014176:Protein Biosynthesis; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D029742:Caenorhabditis elegans Proteins; D005098:Exotoxins; D014157:Transcription Factors; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A