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 μg 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.

The tick saliva immunosuppressor, Salp15, contributes to Th17-induced pathology during Experimental Autoimmune Encephalomyelitis

“…Salp15 has been shown to prevent the development of ovalbumin-induced asthma in mice [5] and of KLH-specific antibody and DTH responses [1] through the specific inhibition of CD4 + T cell activation. We thus hypothesized that the administration of the tick salivary protein during induction of murine EAE would prevent the activation of myelin-specific CD4 + T cells and the development of disease.…”

“…The interaction results in a conformational change of CD4 that impedes the proper activation of the Src kinase, Lck [3], leading to the inhibition of early signaling cascades [2,4]. In vivo, Salp15 prevents the development of acute asthma in ovalbumin-induced mice [5] and the development of antibody and delayed-type sensitivity responses in KLH-immunized animals [1]. Thus, Salp15 has potential beneficial use in conditions in which CD4 + T cells are involved, including autoimmune diseases in which CD4 + T cells are major players.…”

“…Because Salp15 is able to prevent the activation of antigen-specific CD4 + T cells in vivo [1,5] and prevent inflammation in a murine model of asthma [5], we postulated that the administration of the protein during the induction of EAE in mice would prevent the generation of autoreactive T cells and the development of CNS inflammation. Our results show that surprisingly, Salp15 induces the increased differentiation of Th17 effector cells both in vivo and in vitro.…”

Insight into the sialome of the castor bean tick, Ixodes ricinus

“…From this point of view, tick saliva is a rich source of medical compounds. As an example, the immunosuppressive tick salivary protein Salp 15 was shown to suppress the development of experimental asthma in mice [28] and, as an immunosuppressor, Salp 15 is believed to become useful during allogenic transplantation [29]. …”

Silencing of c-kit with small interference RNA attenuates inflammation in a murine model of allergic asthma

“…The experimental model of asthma was generated as previously described (8). Briefly, mice were sensitized by administering ovalbumin (OVA, 20 µg, grade V; SigmaAldrich) with aluminum hydroxide (alum, 2.2� mg; Imject Alum; Pierce Biotechnology, Inc.) in a 100 µl total volume via intraperitoneal (i.p.)…”