title: Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut.
abstract: Typically, immune responses control the pathogen, while repair and stress pathways limit damage caused by pathogenesis. The relative contribution of damage to the outcome of pathogenesis and the mechanistic links between the immune and repair pathways are poorly understood. Here, we analyze how the entomopathogenic bacterium Pseudomonas entomophila induces irreversible damage to the Drosophila gut. We find that P. entomophila ingestion induces a global translational blockage that impairs both immune and repair programs in the fly gut. P. entomophila-induced translational inhibition is dependent on bacterial pore forming toxins and reactive oxygen species produced by the host in response to infection. Translational arrest is mediated through activation of the GCN2 kinase and inhibition of the TOR pathway as a consequence of host damage. Together, our study draws a model of pathogenesis in which bacterial inhibition of translation by excessive activation of stress responsive pathways inhibits both immune and regenerative epithelial responses.
authors: Global Health Institute, School of Life Science, Ecole Polytechnique Federale de Lausanne, Switzerland.
authors: Sveta
authors: S
authors: Chakrabarti
authors: Peter
authors: P
authors: Liehl
authors: Nicolas
authors: N
authors: Buchon
authors: Bruno
authors: B
authors: Lemaitre
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D004847:Epithelial Cells / Q000382:microbiology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011549:Pseudomonas / Q000472:pathogenicity*; D011552:Pseudomonas Infections / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction
chemical_list: D001427:Bacterial Toxins; D029721:Drosophila Proteins; D015852:Eukaryotic Initiation Factor-2; D047908:Intracellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; C410006:Thor protein, Drosophila; C523914:AMPKalpha protein, Drosophila; D055372:AMP-Activated Protein Kinases