title: Ex vivo genome-wide RNAi screening of the Drosophila Toll signaling pathway elicited by a larva-derived tissue extract.
abstract: Damage-associated molecular patterns (DAMPs), so-called "danger signals," play important roles in host defense and pathophysiology in mammals and insects. In Drosophila, the Toll pathway confers damage responses during bacterial infection and improper cell-fate control. However, the intrinsic ligands and signaling mechanisms that potentiate innate immune responses remain unknown. Here, we demonstrate that a Drosophila larva-derived tissue extract strongly elicits Toll pathway activation via the Toll receptor. Using this extract, we performed ex vivo genome-wide RNAi screening in Drosophila cultured cells, and identified several signaling factors that are required for host defense and antimicrobial-peptide expression in Drosophila adults. These results suggest that our larva-derived tissue extract contains active ingredients that mediate Toll pathway activation, and the screening data will shed light on the mechanisms of damage-related Toll pathway signaling in Drosophila.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanoh
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan; PRESTO, Japan Science and Technology Agency, Tokyo, Japan. Electronic address: takayuki.kuraishi@gmail.com.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuraishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Tong
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagata
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: kurata@mail.pharm.tohoku.ac.jp.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kurata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays; D007113:Immunity, Innate; D007814:Larva / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D057790:Staphylococcus saprophyticus / Q000276:immunology; D014020:Tissue Extracts / Q000737:chemistry / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; C499312:Myd88 protein, Drosophila; D011971:Receptors, Immunologic; D014020:Tissue Extracts; D051193:Toll-Like Receptors; C084727:tub protein, Drosophila; D008156:Luciferases; C079896:pll protein, Drosophila; D017346:Protein Serine-Threonine Kinases
keywords: Danger signals; Drosophila; Innate immunity; Sterile inflammation; Toll pathway