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    Toll family members bind multiple Spatzle proteins and activate antimicrobial peptide gene expression in Drosophila

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    J._Biol._Chem._2019_Chowdhury_ ...
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    Authors
    Chowdhury, Munmun
    Li, Chun-Feng
    He, Zhen
    Lu, Yuzhen
    Liu, Xu-Sheng
    Wang, Yu-Feng
    Ip, Y. Tony
    Strand, Michael R.
    Yu, Xiao-Qiang
    UMass Chan Affiliations
    Program in Molecular Medicine
    Document Type
    Journal Article
    Publication Date
    2019-05-14
    Keywords
    Spätzle
    antimicrobial peptide (AMP)
    cytokine response
    gene regulation
    insect immunity
    sex-specific difference
    signal transduction
    toll receptor
    Amino Acids, Peptides, and Proteins
    Biochemistry
    Hemic and Immune Systems
    Immunology and Infectious Disease
    Molecular Biology
    Viruses
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    Abstract
    The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spatzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well understood. Here, we conducted in vitro assays in the Drosophila S2 cell line with the Toll/interleukin-1 receptor (TIR) homology domains of each Toll family member to determine if they can activate a known target of Toll-1, the promoter of the antifungal peptide gene drosomycin. All TIR family members activated the drosomycin promoter, with Toll-1 and Toll-7 TIRs producing the highest activation. We found that the Toll-1 and Toll-7 ectodomains bind Spz-1, -2, and -5 and also vesicular stomatitis virus (VSV) virions, and that Spz-1, -2, -5, and VSV all activated the promoters of drosomycin and several other AMP genes in S2 cells expressing full-length Toll-1 or Toll-7. In vivo experiments indicated that Toll-1 and Toll-7 mutants could be systemically infected with two bacterial species (Enterococcus faecalis and Pseudomonas aeruginosa), the opportunistic fungal pathogen Candida albicans and VSV with different survival in adult females and males compared with wild-type fly survival. Our results suggest that all Toll family members can activate several AMP genes. Our results further indicate that Toll-1 and Toll-7 bind multiple Spz proteins and also VSV, but differentially affect adult survival after systemic infection, potentially because of sex-specific differences in Toll-1 and Toll-7 expression.
    Source

    J Biol Chem. 2019 May 14. pii: jbc.RA118.006804. doi: 10.1074/jbc.RA118.006804. [Epub ahead of print] Link to article on publisher's site

    DOI
    10.1074/jbc.RA118.006804
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/41059
    PubMed ID
    31088910
    Related Resources

    Link to Article in PubMed

    Rights
    © 2019 by The American Society for Biochemistry and Molecular Biology, Inc. Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://www.jbc.org/site/misc/edpolicy.xhtml#copyright.
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.RA118.006804
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