title: The tick salivary protein, Salp15, inhibits the development of experimental asthma.
abstract: Activation of Th2 CD4(+) T cells is necessary and sufficient to elicit allergic airway disease, a mouse model with many features of human allergic asthma. Effectively controlling the activities of these cells could be a panacea for asthma therapy. Blood-feeding parasites have devised remarkable strategies to effectively evade the immune response. For example, ticks such as Ixodes scapularis, which must remain on the host for up to 7 days to feed to repletion, secrete immunosuppressive proteins. Included among these proteins is the 15-kDa salivary protein Salp15, which inhibits T cell activation and IL-2 production. Our objective for these studies was to evaluate the T cell inhibitory properties of Salp15 in a mouse model of allergic asthma. BALB/cJ mice were Ag sensitized by i.p. injection of OVA in aluminum hydroxide, with or without 50 mug of Salp15, on days 0 and 7. All mice were challenged with aerosolized OVA on days 14-16 and were studied on day 18. Compared with control mice sensitized with Ag, mice sensitized with Ag and Salp15 displayed significantly reduced airway hyperresponsiveness, eosinophilia, Ag-specific IgG1 and IgE, mucus cell metaplasia, and Th2 cytokine secretion in vivo and by CD4(+) T cells restimulated with Ag in vitro. Our results demonstrate that Salp15 can effectively prevent the generation of a Th2 immune response and the development of experimental asthma. These studies, and those of others, support the notion that a lack of ectoparasitism may contribute to the increasing prevalence of allergic asthma.
authors.affiliation: Department of Medicine, Vermont Lung Center and University of Vermont, Burlington, VT 05405, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Paveglio
authors.forename: Jenna
authors.initials: J
authors.lastname: Allard
authors.forename: Jana
authors.initials: J
authors.lastname: Mayette
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Whittaker
authors.forename: Ignacio
authors.initials: I
authors.lastname: Juncadella
authors.forename: Juan
authors.initials: J
authors.lastname: Anguita
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018884:Ixodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D018793:Interleukin-13; D015848:Interleukin-5; D012471:Salivary Proteins and Peptides; C464566:Salp15 protein, Ixodes scapularis; D015847:Interleukin-4