Salivating for knowledge: potential pharmacological agents in tick saliva

Abstract

Joppe Hovius and colleagues review anticoagulant and immunosuppressive proteins present in tick saliva, and discuss how immunologically targeting such molecules could prevent transmission of tick-borne pathogens.

Figure 1. Schematic Overview of the Coagulation Cascade

The two major amplification loops in the coagulation cascade are depicted. The first amplification loop consists of TF-FVIIa-mediated factor IX (FIX) activation, which leads to the generation of more FXa. A second amplification loop is formed by the activation of factor XI (FXIa) by thrombin, which results in more activated FIX (FIXa), and, subsequently, additional FXa generation. The right panel indicates how selected tick proteins exert their anticoagulant effect. FIIa, activated factor II; FVa, activated factor V; FVIIIa, activated factor VIII.

Figure 2. Diagram Showing How an Anti-Salp15 Vaccine Could Prevent Transmission of B. burgdorferi

During tick feeding and early mammalian infection, B. burgdorferi expresses OspC, which binds to Salp15 in tick saliva. This binding acts as a shield and protects the spirochete from killing by the host. In addition, Salp15 has been shown to directly inhibit dendritic cell and T cell activation, which could facilitate tick feeding. Salp15 antibodies are likely to bind to Salp15 that has previously bound to OspC on the surface of B. burgdorferi in the tick salivary gland and could thereby enhance clearance by host phagocytic immune cells. Obviously, the Salp15 antibodies would need to recognize a Salp15 epitope other than the epitope that is required for binding of Salp15 to OspC. Similarly, if anti-Salp15 antibodies were to bind to free Salp15, they could neutralize the immunosuppressive effects of Salp15, which could hamper tick feeding and thereby transmission of B. burgdorferi from the tick to the host. Lastly, if anti-Salp15 antibodies were to inhibit binding of Salp15 to Borrelia OspC, this would render the spirochete susceptible to pre-existing or newly generated immunoglobulins. Importantly, Salp15 was originally identified by screening of a tick salivary gland cDNA expression library with tick immune rabbit sera, suggesting that antibodies against Salp15 may participate in tick rejection. DC, dendritic cell; MHC, major histocompatibility complex; MF, macrophage; TCR, T cell receptor.