title: TGF-β signaling regulates resistance to parasitic nematode infection in Drosophila melanogaster.
abstract: Over the past decade important advances have been made in the field of innate immunity; however, our appreciation of the signaling pathways and molecules that participate in host immune responses to parasitic nematode infections lags behind that of responses to microbial challenges. Here we have examined the regulation and immune activity of Transforming Growth Factor-beta (TGF-β) signaling in the model host Drosophila melanogaster upon infection with the nematode parasites Heterorhabditis gerrardi and H. bacteriophora containing their mutualistic bacteria Photorhabdus. We have found that the genes encoding the Activin and Bone Morphogenic Protein (BMP) ligands Dawdle (Daw) and Decapentaplegic (Dpp) are transcriptionally induced in flies responding to infection with the nematode parasites, containing or lacking their associated bacteria. We also show that deficient Daw or Dpp regulates the survival of D. melanogaster adults to the pathogens, whereas inactivation of Daw reduces the persistence of the nematodes in the mutant flies. These findings demonstrate a novel role for the TGF-β signaling pathways in the host anti-nematode immune response. Understanding the molecular mechanisms of host anti-nematode processes will potentially lead to the development of novel means for the efficient control of parasitic nematodes.
authors.affiliation: Department of Biological Sciences, The George Washington University, Washington, DC, USA. Electronic address: ioannise@gwu.edu.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Eleftherianos
authors.affiliation: Department of Biological Sciences, The George Washington University, Washington, DC, USA; Laboratory of Malaria and Vector Research, National Institutes of Health, MD, USA.
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Castillo
authors.affiliation: Department of Biological Sciences, The George Washington University, Washington, DC, USA.
authors.forename: Jelena
authors.initials: J
authors.lastname: Patrnogic
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000469:parasitology*; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D009348:Nematoda / Q000276:immunology* / Q000382:microbiology; D009349:Nematode Infections / Q000276:immunology*; D020637:Photorhabdus; D015398:Signal Transduction; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; C517156:Daw protein, Drosophila; D029721:Drosophila Proteins; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; D028341:Activins
keywords: Immunity; Infection; TGF-β