title: A quantitative genome-wide RNAi screen in C. elegans for antifungal innate immunity genes.
abstract: Caenorhabditis elegans has emerged over the last decade as a useful model for the study of innate immunity. Its infection with the pathogenic fungus Drechmeria coniospora leads to the rapid up-regulation in the epidermis of genes encoding antimicrobial peptides. The molecular basis of antimicrobial peptide gene regulation has been previously characterized through forward genetic screens. Reverse genetics, based on RNAi, provide a complementary approach to dissect the worm's immune defenses.
  
  
  
  We report here the full results of a quantitative whole-genome RNAi screen in C. elegans for genes involved in regulating antimicrobial peptide gene expression. The results will be a valuable resource for those contemplating similar RNAi-based screens and also reveal the limitations of such an approach. We present several strategies, including a comprehensive class clustering method, to overcome these limitations and which allowed us to characterize the different steps of the interaction between C. elegans and the fungus D. coniospora, leading to a complete description of the MAPK pathway central to innate immunity in C. elegans. The results further revealed a cross-tissue signaling, triggered by mitochondrial dysfunction in the intestine, that suppresses antimicrobial peptide gene expression in the nematode epidermis.
  
  
  
  Overall, our results provide an unprecedented system's level insight into the regulation of C. elegans innate immunity. They represent a significant contribution to our understanding of host defenses and will lead to a better comprehension of the function and evolution of animal innate immunity.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.|Present address: Institut de Biologie du Développement de Marseille, CNRS, UMR6216, Case 907, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Zugasti
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.
authors.forename: Nishant
authors.initials: N
authors.lastname: Thakur
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Belougne
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.|Present address: Section of Hematology/Oncology, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Squiban
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.|Present address: Institut de Biologie du Développement de Marseille, CNRS, UMR6216, Case 907, Marseille, France.
authors.forename: C Léopold
authors.initials: CL
authors.lastname: Kurz
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.|Present address: Institut de Genomique Fonctionnelle, 141, rue de la Cardonille, 34094, Montpellier Cedex 05, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Soulé
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.
authors.forename: Shizue
authors.initials: S
authors.lastname: Omi
authors.affiliation: Institut de Mathématiques de Marseille, Aix Marseille Université, I2M Centrale Marseille, CNRS UMR 7373, 13453, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tichit
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France. pujol@ciml.univ-mrs.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France. ewbank@ciml.univ-mrs.fr.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000276:immunology*; D003001:Cloning, Molecular; D004817:Epidermis / Q000276:immunology; D056726:Genetic Association Studies; D049751:Genome, Helminth; D054884:Host-Pathogen Interactions; D006999:Hypocreales; D007113:Immunity, Innate / Q000235:genetics*; D008928:Mitochondria / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Bioinformatics; Databases; Epistasis; Functional genomics; Fungal pathogen; High-throughput screening; Mitochondrial unfolded protein response; Networks; Osmotic stress; Signal transduction