The Tick Salivary Protein, Salp15, Inhibits the Development of Experimental Asthma

• Published in: The Journal of immunology (1950) 2007-06, Vol.178 (11), p.7064-7071
• Main Authors: Paveglio, Sara A, Allard, Jenna, Mayette, Jana, Whittaker, Laurie A, Juncadella, Ignacio, Anguita, Juan, Poynter, Matthew E
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - metabolism; Adjuvants, Immunologic - therapeutic use; Animals; Asthma - immunology; Asthma - pathology; Asthma - prevention & control; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - prevention & control; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - parasitology; Disease Models, Animal; Female; Inflammation Mediators - administration & dosage; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - therapeutic use; Interleukin-13 - antagonists & inhibitors; Interleukin-13 - biosynthesis; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - biosynthesis; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - biosynthesis; Ixodes - immunology; Ixodes scapularis; Ixodidae; Mice; Mice, Inbred BALB C; Mucus - immunology; Mucus - metabolism; Mucus - parasitology; Salivary Proteins and Peptides - administration & dosage; Salivary Proteins and Peptides - metabolism; Salivary Proteins and Peptides - therapeutic use
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.178.11.7064

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.