Chemical Equilibrium at the Tick–Host Feeding Interface:A Critical Examination of Biological Relevance in Hematophagous Behavior

Abstract

Ticks secrete hundreds to thousands of proteins into the feeding site, that presumably all play important functions in the modulation of host defense mechanisms. The current review considers the assumption that tick proteins have functional relevance during feeding. The feeding site may be described as a closed system and could be treated as an ideal equilibrium system, thereby allowing modeling of tick–host interactions in an equilibrium state. In this equilibrium state, the concentration of host and tick proteins and their affinities will determine functional relevance at the tick–host interface. Using this approach, many characterized tick proteins may have functional relevant concentrations and affinities at the feeding site. Conversely, the feeding site is not an ideal closed system, but is dynamic and changing, leading to possible overestimation of tick protein concentration at the feeding site and consequently an overestimation of functional relevance. Ticks have evolved different possible strategies to deal with this dynamic environment and overcome the barrier that equilibrium kinetics poses to tick feeding. Even so, cognisance of the limitations that equilibrium binding place on deductions of functional relevance should serve as an important incentive to determine both the concentration and affinity of tick proteins proposed to be functional at the feeding site.

Quantitative Visions of Reality at the Tick-Host Interface: Biochemistry, Genomics, Proteomics, and Transcriptomics as Measures of Complete Inventories of the Tick Sialoverse

“…Our insights into salivary gland complexity were heavily skewed at this point in time by the limited number of functions known (Mans and Neitz, 2004b). Even so, we still remain with very few empirically confirmed functions to date (Mans, 2019), although function assignment by homology allowed thousands of potential functions to be assigned to tick proteins (Mans et al, 2016;Pienaar et al, 2018;Ribeiro and Mans, 2020).…”

“…The core genetic component comprises not only the genome, but its translational aspects such as the transcriptome and proteome, which are more dynamic in nature, since the final products such as mRNA, proteins and other metabolites show tissue-specific and temporal expression patterns, different half-life's and concentration levels. The impact of concentration levels of proteins and metabolites at the tick feeding site has recently been explored and shown to be critical for effective functioning (Mans, 2019 ). An extensive summary of functions for tick proteins involved at the tick-host interface was also presented previously (Mans, 2016 , 2019 ; Mans et al, 2016 ).…”

“…The impact of concentration levels of proteins and metabolites at the tick feeding site has recently been explored and shown to be critical for effective functioning (Mans, 2019 ). An extensive summary of functions for tick proteins involved at the tick-host interface was also presented previously (Mans, 2016 , 2019 ; Mans et al, 2016 ). The acquisition of new functions by gene duplication has also been explored and shown to play an important part in the expansion of gene families in ticks (Mans et al, 2017 ).…”

Tick and Host Derived Compounds Detected in the Cement Complex Substance

“…Ixodid ticks feed on blood for a relatively long period and an evolutionary adaptation to overcome host inflammatory and immune responses using molecules produced in tick salivary glands or recycled from the host and inoculated with saliva into the feeding site [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Cattle tick Rhipicephalus microplus (Canestrini, 1888) is an Ixodid one-host tick species (all developmental stages remain on the same host) with an impact on cattle industry in tropical and subtropical regions of the world [3,9,10].…”

The Central Role of Salivary Metalloproteases in Host Acquired Resistance to Tick Feeding

“…Ticks salivate proteinaceous saliva into the host during the course of feeding (Francischetti et al, 2009). The individual protein components are secreted into a feeding site at functional concentrations and with adequate affinities for host targets to establish biomolecular associations at the feeding site, thereby modulating host intrinsic hemostatic processes and defence responses (Mans, 2019). To escape immune recognition by the host, tick salivary proteins have evolved low immunogenicity (Chmelar et al, 2016), leading to low or no tick rejection reactions when Ixodes ricinus ticks feed on their natural hosts such as mice, voles, or passerine birds (Dizij and Kurtenbach, 1995;Dusbabek et al, 1995;Heylen et al, 2010).…”