Leukocyte recruitment is a central characteristic of inflammation and is mediated by chemokine proteins binding and activating chemokine receptors expressed on leukocytes1,2. However, in various diseases, chemokines can be overexpressed, giving rise to excessive or inappropriate recruitment of specific leukocyte subsets. As such, inhibition of these chemokines represents a promising approach towards targeted treatment of inflammatory diseases3.
Recently, it has been discovered that the Brown Dog Tick (Rhipicephalus sanguineus) produces three salivary glycoproteins named “evasins” that bind to host chemokines in order to inhibit the host inflammatory response, thereby allowing the tick to obtain a blood meal without being detected by the host4. Using bioinformatics tools, more than 250 putative evasin sequences have been identified based on sequence similarity to the three known evasin glycoproteins. These evasin candidates are derived from a wide variety of hard tick species, spanning the genera Rhipicephalus, Amblyomma and Ixodes, indicating this conserved functionality to be of significant importance. Nine representative sequences were chosen for functional validation of these proposed chemokine binding proteins. Through the use of sequence alignments the evasins were classified into two subfamilies: C8 evasins that share a conserved set of eight Cys residues (four disulfide bonds), and C6 evasins that only possess three disulfide bonds. These candidates were successfully expressed in E. coli and eight of the nine candidates exhibited high affinity binding to human chemokines, thereby validating the hypothesis that they act as chemokine binding proteins.
These putative evasins now serve as a novel source of anti-inflammatory proteins which may serve as useful starting points for future therapeutic applications.
References: 1) Trends Immunol., 2004, 25, 75. 2) Immunity., 2000, 12, 121. 3) Nat. Immunol., 2001, 2, 108. 4) Front. Immunol., 2016, 7, 208.