Deciphering Biological Processes at the Tick-Host Interface Opens New Strategies for Treatment of Human Diseases

Abstract

Ticks are obligatory blood-feeding ectoparasites, causing blood loss and skin damage in their hosts. In addition, ticks also transmit a number of various pathogenic microorganisms that cause serious diseases in humans and animals. Ticks evolved a wide array of salivary bioactive compounds that, upon injection into the host skin, inhibit or modulate host reactions such as hemostasis, inflammation and wound healing. Modulation of the tick attachment site in the host skin involves mainly molecules which affect physiological processes orchestrated by cytokines, chemokines and growth factors. Suppressing host defense reactions is crucial for tick survival and reproduction. Furthermore, pharmacologically active compounds in tick saliva have a promising therapeutic potential for treatment of some human diseases connected with disorders in hemostasis and immune system. These disorders are often associated to alterations in signaling pathways and dysregulation or overexpression of specific cytokines which, in turn, affect mechanisms of angiogenesis, cell motility and cytoskeletal regulation. Moreover, tick salivary molecules were found to exert cytotoxic and cytolytic effects on various tumor cells and have anti-angiogenic properties. Elucidation of the mode of action of tick bioactive molecules on the regulation of cell processes in their mammalian hosts could provide new tools for understanding the complex changes leading to immune disorders and cancer. Tick bioactive molecules may also be exploited as new pharmacological inhibitors of the signaling pathways of cytokines and thus help alleviate patient discomfort and increase patient survival. We review the current knowledge about tick salivary peptides and proteins that have been identified and functionally characterized in in vitro and/or in vivo models and their therapeutic perspective.

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

“…This includes Amblyomin-X, Ir-CPI, TAP, OmCI, and Ra-HBP, among others. Most of these molecules have been described as anti-hemostatic and anti-tumor candidates ( 55 ). Only OmCI and Ra-HBP target immune responses, therefore, their potential applications will be discussed later in this review.…”

Salp15, a Multifunctional Protein From Tick Saliva With Potential Pharmaceutical Effects

“…Collectively, the interaction of Salp15 with DC-SIGN directly modulates the production of cytokines and T cell activation, which is induced by DCs. The properties of Salp15 in modulating human immune responses, especially those of DCs, may provide novel treatment possibilities (82). The DCs are usually present in tissues that make contact with the external environment, such as the skin, nasal mucosa, and intestines.…”

“…Arthropod-based therapeutics are still in their infancy compared with plant-based or microorganism-based therapeutic agents (127). A variety of biologically active substances derived from tick saliva may be valuable resources for the treatment of various diseases (82). Although Salp15 has not yet advanced to preclinical research, its pluripotent effects suggest it may be an attractive candidate for use in immunotherapy.…”

Partial Characterization of Thrombin Inhibitor(s) Derived from Salivary Glands of the Tick, <i>Hyalomma dromedarii</i>, and Related Anti-Cancer Potential

“…Ticks have evolved an array of anti-hemostatic agents including vasodilators, platelet aggregation inhibitors and anticoagulants [3] [4]. It is crucial for ticks to target proteases of the coagulation cascade in order to prevent clot formation and to retain blood fluidity not only in the micro-hematoma at the bite site but also in their mouthparts and midgut until repletion [5].…”