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.
Keywords:
Danger signals; Drosophila; Innate immunity; Sterile inflammation; Toll pathway.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology
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Animals
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Antigens, Differentiation / genetics
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Antigens, Differentiation / immunology
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Antimicrobial Cationic Peptides / biosynthesis
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Antimicrobial Cationic Peptides / immunology*
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Cells, Cultured
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Drosophila Proteins / genetics
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Drosophila Proteins / immunology
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Drosophila melanogaster / genetics
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Drosophila melanogaster / immunology*
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Drosophila melanogaster / microbiology
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Gene Expression Regulation
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Genes, Reporter
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High-Throughput Screening Assays
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Immunity, Innate
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Larva / chemistry
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Larva / genetics
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Larva / immunology
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Larva / microbiology
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Luciferases / genetics
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Luciferases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / immunology
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RNA Interference
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Signal Transduction / immunology*
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Staphylococcus saprophyticus / immunology
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Tissue Extracts / chemistry
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Tissue Extracts / immunology
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Toll-Like Receptors / genetics
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Toll-Like Receptors / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Antimicrobial Cationic Peptides
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Drosophila Proteins
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Myd88 protein, Drosophila
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Receptors, Immunologic
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Tissue Extracts
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Toll-Like Receptors
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tub protein, Drosophila
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Luciferases
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pll protein, Drosophila
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Protein Serine-Threonine Kinases