Tick saliva in anti-tick immunity and pathogen transmission

Kovář, Lubomír

doi:10.1007/bf02931051

Cited by 38 publications

(19 citation statements)

References 113 publications

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“…In haematophagous ectoparasites such as ticks, salivary modulators of the host DC have presumably evolved to suppress the host immune response to facilitate blood feeding (reviewed in Kovár, 2004; Schwarz et al, 2012; Kazimírová and Štibrániová, 2013). For those species that are vectors of pathogens, such molecules could also create a permissive environment for pathogen transmission (Preston et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

Zavašnik–Bergant

Vidmar

Sekirnik

et al. 2017

Front. Cell. Infect. Microbiol.

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To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 from Ornithodoros moubata was studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin. Following internalization, cystatin OmC2 was initially found to inhibit the activity of several cysteine cathepsins, as indicated by the decreased rates of degradation of fluorogenic peptide substrates. To identify targets, affinity chromatography was used to isolate His-tagged cystatin OmC2 together with the bound proteins from MUTZ-3 cells. Cathepsins S and C were identified in these complexes by mass spectrometry and confirmed by immunoblotting. Furthermore, reduced increase in the surface expression of MHC II and CD86, which are associated with the maturation of dendritic cells, was observed. In contrast, human inhibitor cystatin C, which is normally expressed and secreted by dendritic cells, did not affect the expression of CD86. It is proposed that internalization of salivary cystatin OmC2 by the host dendritic cells targets cathepsins S and C, thereby affecting their maturation.

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Section: Discussionmentioning

confidence: 99%

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

Zavašnik–Bergant

Vidmar

Sekirnik

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Over the years several lines of research have attempted to replicate these studies through immunization of animals with crude tick saliva gland protein extracts (Brown et al, 1984, Shapiro et al, 1989, Nyindo et al, 1989, Banerjee et al, 1990, Kovar, 2004, Willadsen, 2006, Narasimhan et al, 2007, Jittapalapong et al, 2008) and since the 1990s with recombinant tick saliva proteins (Tsuda et al, 2001, Mulenga et al, 1999, You, 2005, Dai et al, 2009, Guo et al, 2009). The common practice in tick vaccine efficacy studies is to challenge infests immunized animals once (Tsuda et al, 2001, Mulenga et al, 1999, You, 2005, Dai et al, 2009, Guo et al, 2009, Galay et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Target validation of highly conserved Amblyomma americanum tick saliva serine protease inhibitor 19

Kim

Radulović

Mulenga

2016

Ticks and Tick-borne Diseases

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Amblyomma americanum tick serine protease inhibitor (serpin, AAS) 19, is a highly conserved protein that is characterized by its functional domain being 100% conserved across tick species. We also reported that AAS19 was an immunogenic tick saliva protein with anti-haemostatic functions and an inhibitor of trypsin-like proteases including five of the eight serine protease factors in the blood clotting cascade. In this study the goal was to validate the importance of AAS19 in A. americanum tick physiology, assess immunogenicity and investigate tick vaccine efficacy of yeast-expressed recombinant (r) AAS19. We confirm that AAS19 is important to A. americanum fitness and blood meal feeding. AAS19 mRNA disruption by RNAi silencing caused ticks to obtain blood meals that were 50% smaller than controls, and treated ticks being morphologically deformed with 100% of the deformed ticks dying in incubation. We show that rAAS19 is highly immunogenic in that two 500 µg inoculations mixed with TiterMax Gold adjuvant provoked antibody titers of more than 1:320000 that specifically reacted with native AAS19 in unfed and partially fed tick tissue. Since AAS19 is injected into animals during tick feeding, we challenge infested immunized rabbits twice to test if tick infestations of immunized rabbits could act as booster. While in the first infestation significantly smaller tick blood meals were observed on one of the two immunized rabbits, smaller blood meals were observed on both rabbits, but 60% of ticks that engorged on immunized rabbits in the second infestation failed to lay eggs. It is notable that ticks fed faster on immunized animals despite obtaining smaller blood meals. We conclude that rAAS19 is a potential component of cocktail tick vaccine.

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“…There is also a possibility that A. americanum ticks may not need CRT to bind factor Xa because they have alternatives. Previous studies have reported tick salivary gland anticoagulants that target multiple hemostatic factors including factor Xa (Wang et al, 1996, Mans et al, 2002, Kovář, 2004, Waxman et al, 1990, Limo et al, 1991, Ibrahim et al, 2001, Francischetti et al, 2002). In both of the plasma clotting assays (APPT and RCT) used in this study plasma clotting was triggered by addition of CaCl 2 .…”

Section: Discussionmentioning

confidence: 99%

Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade

Kim

Ibelli

Mulenga

2015

Ticks and Tick-borne Diseases

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In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it’s plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it’s current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation aggregation. We discuss our findings in the context of tick feeding physiology.

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Tick saliva in anti-tick immunity and pathogen transmission

Cited by 38 publications

References 113 publications

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

Target validation of highly conserved Amblyomma americanum tick saliva serine protease inhibitor 19

Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade

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