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dc.contributor.authorChowdhury, Munmun
dc.contributor.authorLi, Chun-Feng
dc.contributor.authorHe, Zhen
dc.contributor.authorLu, Yuzhen
dc.contributor.authorLiu, Xu-Sheng
dc.contributor.authorWang, Yu-Feng
dc.contributor.authorIp, Y. Tony
dc.contributor.authorStrand, Michael R.
dc.contributor.authorYu, Xiao-Qiang
dc.date2022-08-11T08:09:53.000
dc.date.accessioned2022-08-23T16:47:20Z
dc.date.available2022-08-23T16:47:20Z
dc.date.issued2019-05-14
dc.date.submitted2019-06-21
dc.identifier.citation<p>J Biol Chem. 2019 May 14. pii: jbc.RA118.006804. doi: 10.1074/jbc.RA118.006804. [Epub ahead of print] <a href="https://doi.org/10.1074/jbc.RA118.006804">Link to article on publisher's site</a></p>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.RA118.006804
dc.identifier.pmid31088910
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41059
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31088910&dopt=Abstract">Link to Article in PubMed</a></p>
dc.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.
dc.subjectSpätzle
dc.subjectantimicrobial peptide (AMP)
dc.subjectcytokine response
dc.subjectgene regulation
dc.subjectinsect immunity
dc.subjectsex-specific difference
dc.subjectsignal transduction
dc.subjecttoll receptor
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectHemic and Immune Systems
dc.subjectImmunology and Infectious Disease
dc.subjectMolecular Biology
dc.subjectViruses
dc.titleToll family members bind multiple Spatzle proteins and activate antimicrobial peptide gene expression in Drosophila
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4865&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3850
dc.legacy.embargo2020-05-14T00:00:00-07:00
dc.identifier.contextkey14784759
refterms.dateFOA2022-08-23T16:47:20Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/3850
dc.contributor.departmentProgram in Molecular Medicine


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