Immunomodulatory Proteins in Tick Saliva From a Structural Perspective

Abstract

To feed successfully, ticks must bypass or suppress the host’s defense mechanisms, particularly the immune system. To accomplish this, ticks secrete specialized immunomodulatory proteins into their saliva, just like many other blood-sucking parasites. However, the strategy of ticks is rather unique compared to their counterparts. Ticks’ tendency for gene duplication has led to a diverse arsenal of dozens of closely related proteins from several classes to modulate the immune system’s response. Among these are chemokine-binding proteins, complement pathways inhibitors, ion channels modulators, and numerous poorly characterized proteins whose functions are yet to be uncovered. Studying tick immunomodulatory proteins would not only help to elucidate tick-host relationships but would also provide a rich pool of potential candidates for the development of immunomodulatory intervention drugs and potentially new vaccines. In the present review, we will attempt to summarize novel findings on the salivary immunomodulatory proteins of ticks, focusing on biomolecular targets, structure-activity relationships, and the perspective of their development into therapeutics.

Current status of structural studies of proteins originating from Arachnida

“…In summary, currently, the Arachnida proteins are of significant interest for biomedical, agricultural and material sciences, but are significantly understudied. Based on this review, the proteins or peptides studies are not very diverse and can be categorized mainly as toxins, spidroins, salivary proteins, and allergens (Fernández-Caldas et al 2014;Wang et al 2014;Thomas 2015;Daly & Wilson 2018;Bhusal et al 2020;Denisov & Dijkgraaf 2021). We conclude that structural studies of Arachnida-derived proteins are in their infancy, because of the importance of Arachnid proteins not only from the perspective of human health or biomaterials but also from potential application in agriculture.…”

“…Ticks are the final group described here that contributes a significant fraction of the PDB deposits from Arachnida. In the case of this group, proteins derived from Ixodidae (hard ticks) are the most often studied, and the research generally concentrates on ticks' salivary proteins and their role in the transfer of various pathogens (Denisov & Dijkgraaf 2021). Given the significance of tick saliva in host immune defense modulation, these proteins exhibit crucial roles in binding interaction to host receptors (Kazimírová & Štibrániová 2013;Chmelař et al 2019).…”

“…Many enzyme inhibitors, such as serine protease inhibitors (SPIs), have been described. SPIs' importance in several tick biological processes has been shown to be directly involved in the regulation of inflammation, wound healing, vasoconstriction, blood clotting, and the modulation of host defense mechanisms (Blisnick et al 2017;Denisov et al 2021).…”

Peptidomics Analysis Reveals the Buccal Gland of Jawless Vertebrate Lamprey as a Source of Multiple Bioactive Peptides

“…Typical hematophagous animals, including leeches and ticks, contain biologically active compounds in their secretions, especially in the saliva. The components of the salivary glands of leeches and ticks are relatively well studied, and classical active peptides, such as hirudin, have been used widely [25,26]. As bloodsuckers, the buccal glands of lampreys are considered a source of diverse bioactive proteins, from which various anticoagulant-and immune-related proteins, such as RGD (Arg-Gly-Asp) motif toxin and cysteine-rich secretory protein (CRISP), have been identified in recent years [14,27].…”

Host Immune Responses to Salivary Components - A Critical Facet of Tick-Host Interactions

“…Among these, As8.9kDa is known to inactivate the C3b factor, thus inhibiting the downstream cascade ( Costa et al., 2021 ) ( Figure 1 ) . Salivary proteins that inhibit binding of mannan-binding lectin to the polysaccharide mannan were characterized in I. scapularis (TSLPI, Salp1, and Salp9Pac) and O. savignyi (BSAP), resulting in the inactivation of the lectin complement pathway ( Denisov and Dijkgraaf, 2021 ). Other complement pathway inhibitors and their molecular mechanisms require further studies to be properly elucidated.…”