title: Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites.
abstract: The proteolytic activities frequently associated with sources of allergens and parasite secretions have been suggested as important immunomodulators. We have investigated whether the protease activity of the house dust mite allergen Der p1 and the secreted proteases of the hookworm Necator americanus are able to directly induce type 2 cytokine production by basophils. Der p1 and the secretions of N. americanus induced interleukin (IL)-4, IL-5, and IL-13 but not interferon-gamma mRNA in KU812 basophils. Enzyme-linked immunosorbent assay confirmed that IL-4 and IL-13 were secreted. A nonproteolytic antigen failed to induce cytokine expression, and preincubation of Der p1 or N. americanus secretions with protease inhibitors inhibited cytokine expression. Data were confirmed using basophils purified from human peripheral blood. We speculate that this innate mechanism may contribute to the development of a cytokine milieu that could promote immunoglobulin E synthesis, eosinophil recruitment, and the development of type 2 T cells.
authors.affiliation: Department of Microbiology and Immunology, Institute for Lung Health, University of Leicester, University Road, Leicester LE1 9HN, United Kingdom.
authors.forename: Clair
authors.initials: C
authors.lastname: Phillips
authors.forename: William R
authors.initials: WR
authors.lastname: Coward
authors.forename: David I
authors.initials: DI
authors.lastname: Pritchard
authors.forename: Colin R A
authors.initials: CR
authors.lastname: Hewitt
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology; D060829:Arthropod Proteins; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D010450:Endopeptidases / Q000276:immunology* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006376:Helminths / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma; D018793:Interleukin-13 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis; D017221:Necator americanus / Q000201:enzymology / Q000276:immunology; D039981:Pyroglyphidae / Q000201:enzymology* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1