A quantitative genome-wide RNAi screen in C. elegans for antifungal innate immunity genes

BMC Biology

Research Article

Nishant Thakur¹  Jérôme Belougne¹  Nathalie Pujol¹  Shizue Omi¹  Jonathan J. Ewbank¹  C. Léopold Kurz²  Olivier Zugasti²  Julien Soulé³  Barbara Squiban⁴  Laurent Tichit⁵ 

[1] Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France;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;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;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;Institut de Mathématiques de Marseille, Aix Marseille Université, I2M Centrale Marseille, CNRS UMR 7373, 13453, Marseille, France;

关键词: Fungal pathogen;    Functional genomics;    High-throughput screening;    Signal transduction;    Networks;    Osmotic stress;    Epistasis;    Bioinformatics;    Databases;    Mitochondrial unfolded protein response;   

DOI  :  10.1186/s12915-016-0256-3

 received in 2016-01-19, accepted in 2016-04-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCaenorhabditis 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.ResultsWe 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.ConclusionsOverall, 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.

【 授权许可】

CC BY   
© Zugasti et al. 2016