title: Dermatophagoides pteronyssinus major allergen 1 activates the innate immune response of the fruit fly Drosophila melanogaster.
abstract: Some allergens with relevant protease activity have the potential to directly interact with host structures. It remains to be elucidated whether this activity is relevant for developing their allergenic properties. The major goal of this study was to elucidate whether allergens with a strong protease activity directly interact with modules of the innate immune system, thereby inducing an immune response. We chose Drosophila melanogaster for our experiments to prevent the results from being influenced by the adaptive immune system and used the armamentarium of methods available for the fly to study the underlying mechanisms. We show that Dermatophagoides pteronyssinus major allergen 1 (Der p 1), the major allergen of the house dust mite, efficiently activates various facets of the Drosophila innate-immune system, including both epithelial and systemic responses. These responses depend on the immune deficiency (IMD) pathway via activation of the NF-κB transcription factor Relish. In addition, the major pathogen associated molecular pattern recognizing receptor of the IMD pathway, peptidoglycan recognition protein-LC, was necessary for this response. We showed that Der p 1, which has cysteine protease activity, cleaves the ectodomain of peptidoglycan recognition protein-LC and, thus, activates the IMD pathway to induce a profound immune response. We conclude that the innate immune response to this allergen-mediated proteolytic cleavage represents an ancient type of danger signaling that may be highly relevant for the primary allergenicity of compounds such as Der p 1.
authors.affiliation: Department of Immunology and Cell Biology, Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Warmbold
authors.forename: Karin
authors.initials: K
authors.lastname: Uliczka
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Rus
authors.forename: Roland
authors.initials: R
authors.lastname: Suck
authors.forename: Arnd
authors.initials: A
authors.lastname: Petersen
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Thomas
authors.initials: T
authors.lastname: Roeder
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics / Q000502:physiology*; D060829:Arthropod Proteins / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000502:physiology*; D040002:Dermatophagoides pteronyssinus / Q000235:genetics / Q000276:immunology*; D004331:Drosophila melanogaster / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1