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    Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster

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    Authors
    Tanji, Takahiro
    Hu, Xiaodi
    Weber, Alexander N. R.
    Ip, Y. Tony
    UMass Chan Affiliations
    Program in Molecular Medicine
    Document Type
    Journal Article
    Publication Date
    2007-04-18
    Keywords
    Animals
    Animals, Genetically Modified
    Carrier Proteins
    Cells, Cultured
    Drosophila melanogaster
    *Immunity, Natural
    Male
    Signal Transduction
    Toll-Like Receptors
    Life Sciences
    Medicine and Health Sciences
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    Abstract
    The inducible expression of antimicrobial peptide genes in Drosophila melanogaster is regulated by the conserved Toll and peptidoglycan recognition protein LC/immune deficiency (PGRP-LC/IMD) signaling pathways. It has been proposed that the two pathways have independent functions and mediate the specificity of innate immune responses towards different microorganisms. Scattered evidence also suggests that some antimicrobial target genes can be activated by both Toll and IMD, albeit to different extents. This dual activation can be mediated by independent stimulation or by cross-regulation of the two pathways. We show in this report that the Toll and IMD pathways can interact synergistically, demonstrating that cross-regulation occurs. The presence of Spatzle (the Toll ligand) and gram-negative peptidoglycan (the PGRP-LC ligand) together caused synergistic activation of representative target genes of the two pathways, including Drosomycin, Diptericin, and AttacinA. Constitutive activation of Toll and PGRP-LC/IMD could mimic the synergistic stimulation. RNA interference assays and promoter analyses demonstrate that cooperation of different NF-kappaB-related transcription factors mediates the synergy. These results illustrate how specific ligand binding by separate upstream pattern recognition receptors can be translated into a broad-spectrum host response, a hallmark of innate immunity.
    Source
    Mol Cell Biol. 2007 Jun;27(12):4578-88. Epub 2007 Apr 16. Link to article on publisher's site
    DOI
    10.1128/MCB.01814-06
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38464
    PubMed ID
    17438142
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1128/MCB.01814-06
    Scopus Count
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    UMass Chan Faculty and Researcher Publications

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