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Review
. 2021 Oct 13:11:769574.
doi: 10.3389/fcimb.2021.769574. eCollection 2021.

Immunomodulatory Proteins in Tick Saliva From a Structural Perspective

Stepan S Denisov  1 , Ingrid Dijkgraaf  1
Affiliations
Review

Immunomodulatory Proteins in Tick Saliva From a Structural Perspective

Stepan S Denisov et al. Front Cell Infect Microbiol. .

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.

Keywords: immunomodulatory; protein; saliva; structure-activity relationship; ticks.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Binding of chemokines by class A and B evasins. (A) The model of EVA-3/CXCL8 complex. Unstructured N- and C-termini of EVA-3 are hidden for visibility. (B) The crystal structure of EVA-1/CCL3 complex (PDB: 3FPU). Evasins are colored according to a gradient from N- to C-terminus, chemokines are shown in grey and oriented in the same direction.
Figure 2
Figure 2
Tick serpin Iripin-3 (A, PDB: 7AHP) and cystatin Sialostatin L2 (B, PDB: 3LH4) structures colored according to a gradient from N- to C-terminus.
Figure 3
Figure 3
(A) OmCI structure in the complex with ricinoleic acid (PDB: 2CM4). OmCI structure is colored according to a gradient, ricinoleic acids is shown in yellow. (B) The structure of C5 protein in the complex with OmCi, RaCI, and CirpT (PDB: 6RQJ). C5 is shown in grey, tick proteins – in color.
Figure 4
Figure 4
Tick complement inhibitors BSAP1 (A, PDB: 7NE8), RaCI2 (B, PDB: 5IEC), and CirpT (C, PDB: 6RPT). Proteins are colored according to a gradient from N- to C-terminus.
See this image and copyright information in PMC

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