Identification of an IL-2 Binding Protein in the Saliva of the Lyme Disease Vector Tick, Ixodes scapularis

Abstract

A potent inhibitor of mitogen-stimulated T cell proliferation exists in the saliva of several species of hard ticks, including the Lyme disease vector tick, Ixodes scapularis. Our characterization of this phenomenon has led to the identification of a possible mechanism for the T cell inhibitory activity of I. scapularis saliva. The T cell inhibitor can overcome stimulation of mouse spleen cells with anti-CD3 mAb; however, a direct and avid interaction with T cells does not appear to be necessary. Tick saliva inhibits a mouse IL-2 capture ELISA, suggesting that a soluble IL-2 binding factor is present in the saliva. This hypothesis was verified by using a direct binding assay in which plate-immobilized tick saliva was shown to bind both mouse and human IL-2. Elimination of the IL-2 binding capacity of saliva in the in vitro assays by trypsin digestion demonstrated that the IL-2 binding factor is a protein. These experiments comprise the first demonstration of the existence of such a secreted IL-2 binding protein from any parasite or pathogen. This arthropod salivary IL-2 binding capacity provides a simple mechanism for the suppression of T cell proliferation as well as for the activity of other immune effector cells that are responsive to IL-2 stimulation. Relevance of the tick T cell inhibitory activity to the human immune system is demonstrated by the ability of tick saliva to inhibit proliferation of human T cells and CTLL-2 cells grown in the presence of human IL-2.

Disruption of Ixodes scapularis anticoagulation by using RNA interference

“…Characterizations of tick salivary antigens have, therefore, been based on their ability to (i) induce skin hypersensitivity reaction on tick-resistant animals, (ii) react with anti-tick immune serum, (iii) modulate host immune responses, and (iv) thwart host hemostatic mechanisms (28). Although these approaches have identified several tick salivary proteins (11,14,16,23,(28)(29)(30)(31), an effective vaccine against I. scapularis ticks remains elusive. Recently, random sequencing of clones from an adult I. scapularis salivary gland cDNA library identified Ϸ100 I. scapularis genes (17).…”

“…Ixolaris, an inhibitor of the factor X-tissue factor VIIIa complex (11), and Salp14, an inhibitor of factor Xa (12), represent two of the prototypic anticoagulants that have been identified in I. scapularis saliva. Proteins that modulate various host immune responses have been characterized also from ixodid tick saliva (13)(14)(15)(16). Establishing the physiological relevance of these proteins has relied on conventional protein immunization techniques.…”

Dermatologic Changes Induced by RepeatedIxodes scapularisBites and Implications for Prevention of Tick-Borne Infection

“…I. scapularis saliva also reduces the expression of b2-integrin (CD18) that is essential for interactions of human neutrophils with extracellular matrix and decreases the uptake and killing of B. burgdorferi (Montgomery et al 2004). I. scapularis saliva inhibits T-cell proliferation (Urioste et al 1994), contains an interleukin-2 binding protein (Gillespie et al 2001) and polarizes CD4 Tcells to a Th2 cytokine profile (Schoeler et al 1999, Müller-Doblies et al 2007). CD4 ϩ T-cell activation is inhibited by the I. scapularis protein, Salp 15, which binds to extracellular domains of CD4 (Garg et al 2006).…”

An insight into the sialome of the soft tick, Ornithodorus parkeri

“…Accordingly, it is possible that the remaining lipocalins not only may bind small compounds that are physiologically active at lower concentrations, such as prostaglandins and leukotrienes (Calvo et al, 2006), but they may also bind larger cytokines and chemokines. Indeed, uncharacterized cytokine-binding proteins are known to exist in tick saliva (Gillespie et al, 2001;Hajnicka et al, 2001;Hajnicka et al, 2005;Konik et al, 2006). However, a recently described chemokine binding protein from Rhipicephalus sanguineus belongs to a novel protein family (Frauenschuh et al, 2007).…”