tick-host interaction
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Vector-borne diseases constitute 17% of all infectious diseases in the world; among the blood-feeding arthropods, ticks transmit the highest number of pathogens. Understanding the interactions between the tick vector, the mammalian host and the pathogens circulating between them is the basis for the successful development of vaccines against ticks or the tick-transmitted pathogens as well as for the development of specific treatments against tick-borne infections. A lot of effort has been put into transcriptomic and proteomic analyses; however, the protein-carbohydrate interactions and the overall glycobiology of ticks and tick-borne pathogens has not been given the importance or priority deserved. Novel (bio)analytical techniques and their availability have immensely increased the possibilities in glycobiology research and thus novel information in the glycobiology of ticks and tick-borne pathogens is being generated at a faster pace each year. This review brings a comprehensive summary of the knowledge on both the glycosylated proteins and the glycan-binding proteins of the ticks as well as the tick-transmitted pathogens, with emphasis on the interactions allowing the infection of both the ticks and the hosts by various bacteria and tick-borne encephalitis virus.
- MeSH
- Anaplasma patogenita MeSH
- Borrelia patogenita MeSH
- glykomika metody MeSH
- glykosylace MeSH
- interakce hostitele a patogenu fyziologie MeSH
- klíště mikrobiologie fyziologie virologie MeSH
- lektiny metabolismus MeSH
- nemoci přenášené klíšťaty patofyziologie MeSH
- polysacharidy metabolismus MeSH
- proteomika MeSH
- sacharidy fyziologie MeSH
- viry klíšťové encefalitidy patogenita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Tick-borne encephalitis virus (TBEV) is a member of the genus Flavivirus. It can cause serious infections in humans that may result in encephalitis/meningoencephalitis. Although several studies have described the involvement of specific genes in the host response to TBEV infection in the central nervous system (CNS), the overall network remains poorly characterized. Therefore, we investigated the response of DAOY cells (human medulloblastoma cells derived from cerebellar neurons) to TBEV (Neudoerfl strain, Western subtype) infection to characterize differentially expressed genes by transcriptome analysis. Our results revealed a wide panel of interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including type III but not type I (or II) interferons (IFNs), which are activated upon TBEV infection, as well as a number of non-coding RNAs, including long non-coding RNAs. To obtain a broader view of the pathways responsible for eliciting an antiviral state in DAOY cells we examined the effect of type I and III IFNs and found that only type I IFN pre-treatment inhibited TBEV production. The cellular response to TBEV showed only partial overlap with gene expression changes induced by IFN-β treatment - suggesting a virus-specific signature - and we identified a group of ISGs that were highly up-regulated following IFN-β treatment. Moreover, a high rate of down-regulation was observed for a wide panel of pro-inflammatory cytokines upon IFN-β treatment. These data can serve as the basis for further studies of host-TBEV interactions and the identification of ISGs and/or lncRNAs with potent antiviral effects in cases of TBEV infection in human neuronal cells.
- MeSH
- aktivace transkripce MeSH
- cytokiny genetika imunologie MeSH
- interakce hostitele a patogenu MeSH
- interferony genetika imunologie MeSH
- klíšťová encefalitida genetika imunologie virologie MeSH
- lidé MeSH
- neurony imunologie virologie MeSH
- viry klíšťové encefalitidy genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The presence of sialylated structures in tick organs was observed previously using lectin staining. Recently, we demonstrated the presence of sialylated N-glycans using mass spectrometry in tick salivary glands and the gut. However, we proposed a host (blood) origin for these glycans and mapped the transport of sialylated molecules from the gut to the salivary glands. In this report, we performed quantitation of whole sialic acid and of metabolically incorporated sialic acid (N-azido neuraminic acid) in Ixodes ricinus tick samples. We show that the majority of sialylated molecules in the adult tick originate in the host (blood) and are not synthesized by the tick. Similar results were observed for tick cell cultures. The almost complete absence of tick sialylated molecules and the specific transport and localization of host structures into the tick salivary glands and the saliva raises many questions on the role of these molecules in the physiology and, specifically, the blood-feeding of ticks.
- MeSH
- buněčné linie MeSH
- glykoproteiny krev metabolismus MeSH
- interakce hostitele a parazita * MeSH
- klíště metabolismus fyziologie MeSH
- kyselina N-acetylneuraminová metabolismus MeSH
- sliny metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
UNLABELLED: Next generation sequencing and proteomics have helped to comprehensively characterize gene expression in tick salivary glands at both the transcriptome and the proteome level. Functional data are, however, lacking. Given that tick salivary secretions are critical to the success of the tick transmission lifecycle and, as a consequence, for host colonization by the pathogens they spread, we thoroughly review here the literature on the known interactions between tick saliva (or tick salivary gland extracts) and the innate and adaptive vertebrate immune system. The information is intended to serve as a reference for functional characterization of the numerous genes and proteins expressed in tick salivary glands with an ultimate goal to develop novel vector and pathogen control strategies. SIGNIFICANCE: We overview all the known interactions of tick saliva with the vertebrate immune system. The provided information is important, given the recent developments in high-throughput transcriptomic and proteomic analysis of gene expression in tick salivary glands, since it may serve as a guideline for the functional characterization of the numerous newly-discovered genes expressed in tick salivary glands.
- MeSH
- hmyzí proteiny imunologie MeSH
- interakce hostitele a parazita imunologie MeSH
- klíšťata imunologie MeSH
- modely imunologické MeSH
- přirozená imunita imunologie MeSH
- sliny imunologie sekrece MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
The hard tick Ixodes ricinus is an important disease vector whose salivary secretions mediate blood-feeding success on vertebrate hosts, including humans. Here we describe the expression profiles and downstream analysis of de novo-discovered microRNAs (miRNAs) expressed in I. ricinus salivary glands and saliva. Eleven tick-derived libraries were sequenced to produce 67,375,557 Illumina reads. De novo prediction yielded 67 bona fide miRNAs out of which 35 are currently not present in miRBase. We report for the first time the presence of microRNAs in tick saliva, obtaining furthermore molecular indicators that those might be of exosomal origin. Ten out of these microRNAs are at least 100 times more represented in saliva. For the four most expressed microRNAs from this subset, we analyzed their combinatorial effects upon their host transcriptome using a novel in silico target network approach. We show that only the inclusion of combinatorial effects reveals the functions in important pathways related to inflammation and pain sensing. A control set of highly abundant microRNAs in both saliva and salivary glands indicates no significant pathways and a far lower number of shared target genes. Therefore, the analysis of miRNAs from pure tick saliva strongly supports the hypothesis that tick saliva miRNAs can modulate vertebrate host homeostasis and represents the first direct evidence of tick miRNA-mediated regulation of vertebrate host gene expression at the tick-host interface. As such, the herein described miRNAs may support future drug discovery and development projects that will also experimentally question their predicted molecular targets in the vertebrate host.
- MeSH
- genové regulační sítě * MeSH
- infestace klíšťaty genetika parazitologie MeSH
- interakce hostitele a parazita genetika MeSH
- klíště genetika MeSH
- mikro RNA analýza genetika MeSH
- obratlovci parazitologie MeSH
- počítačová simulace MeSH
- slinné žlázy metabolismus MeSH
- sliny chemie metabolismus MeSH
- transkriptom * MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Ticks must durably suppress vertebrate host responses (hemostasis, inflammation, immunity) to avoid rejection and act as vectors of many pathogenic microorganisms that cause disease in humans and animals. Transcriptomics and proteomics studies have been used to study tick-host-pathogen interactions and have facilitated the systematic characterization of salivary composition and molecular dynamics throughout tick feeding. Tick saliva contains a complement of protease inhibitors that are differentially produced during feeding, many of which inhibit blood coagulation, platelet aggregation, vasodilation, and immunity. Here we focus on two major groups of protease inhibitors, the small molecular weight Kunitz inhibitors and cystatins. We discuss their role in tick-host-pathogen interactions, how they mediate the interaction between ticks and their hosts, and how they might be exploited both by pathogens to invade hosts and as candidates for the treatment of various human pathologies.
- MeSH
- aprotinin chemie metabolismus MeSH
- cystatiny chemie metabolismus MeSH
- inhibitory proteas metabolismus MeSH
- interakce hostitele a parazita * MeSH
- klíšťata MeSH
- proteomika MeSH
- slinné žlázy metabolismus MeSH
- sliny metabolismus MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Collection of 1327 ticks sampled throughout Greece, Bulgaria, Romania and Croatia, from 211 tortoises belonging to three species, Testudo marginata Schoepff, T. graeca Linnaeus, and T. hermanni Gmelin, revealed the presence of four species of ixodid ticks, namely Hyalomma aegyptium (Linnaeus), Haemaphysalis sulcata Canestrini and Fanzago, H. inermis Birula and Rhipicephalus sanguineus (Latreille). Study confirmed the strong dominance of all life stages of H. aegyptium among ticks parasitizing west Palaearctic tortoises of genus Testudo Linnaeus. Furthermore, a considerable portion of ticks collected from tortoises in southwestern Bulgaria represent larvae and nymphs of H. sulcata. At the same area we collected as exception one larva and one nymph of H. inermis from a single specimen of T. hermanni. Our findings of four adults of R. sanguineus is the first record of this species from reptilian host. According to our results achieved on localities with syntopic occurrence of two tortoise species, T. marginata and T. graeca represent in the Balkans the principal hosts of H. aegyptium, whereas T. hermanni serves only as an alternative host in the areas close to range of either T. marginata or T. graeca.
- MeSH
- financování organizované MeSH
- infestace klíšťaty epidemiologie parazitologie MeSH
- interakce hostitele a parazita MeSH
- Ixodidae růst a vývoj MeSH
- neparametrická statistika MeSH
- prevalence MeSH
- želvy anatomie a histologie parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Geografické názvy
- Řecko MeSH
- východní Evropa MeSH
BACKGROUND: Ticks counteract host inflammatory responses by secreting proteins from their saliva that compete for histamine binding. Among these tick salivary proteins are lipocalins, antiparallel beta-barrel proteins that sequester small molecules. A tick salivary lipocalin has been structurally resolved and experimentally shown to efficiently compete for histamine with its native receptor (e.g., H1 histamine receptor). To date, molecular dynamics simulations focus on protein-protein and protein-ligand interactions, but there are currently no studies for simultaneous ligand exploration between two competing proteins. METHODS: Aided by state-of-the-art, high-throughput computational methods, the current study simulated and analyzed the dynamics of competitive histamine binding at the tick-host interface using the available crystal structures of both the tick salivary lipocalin histamine-binding protein from Rhipicephalus appendiculatus and the human histamine receptor 1. RESULTS: The attraction towards the tick salivary lipocalin seems to depend on the protonated (adding a hydrogen ion) state of histamine since the current study shows that as histamine becomes more protonated it increases its exploration for the tick salivary lipocalin. This implies that during tick feeding, histamine may need to be protonated for the tick salivary lipocalin to efficiently sequester it in order to counteract inflammation. Additionally, the beta-hairpin loops (at both ends of the tick salivary lipocalin barrel) were reported to have a functional role in sequestering histamine and the results in the current study concur and provide evidence for this hypothesis. These beta-hairpin loops of the tick salivary lipocalin possess more acidic residues than a structurally similar but functionally unrelated lipocalin from the butterfly, Pieris brassicae; comparative results indicate these acidic residues may be responsible for the ability of the tick lipocalin to out-compete the native (H1) receptor for histamine. CONCLUSIONS: Three explanatory types of data can be obtained from the current study: (i) the dynamics of multiple binding sites, (ii) competition between two proteins for a ligand, and (iii) the intrinsic molecular components involved in the competition. These data can provide further insight at the atomic level of the host-tick interface that cannot be experimentally determined. Additionally, the methods used in this study can be applied in rationally designing drugs.
- MeSH
- histamin metabolismus MeSH
- interakce hostitele a patogenu * MeSH
- kinetika MeSH
- lidé MeSH
- lipokaliny chemie metabolismus MeSH
- molekulární modely MeSH
- receptory histaminu H1 chemie metabolismus MeSH
- Rhipicephalus fyziologie MeSH
- simulace molekulární dynamiky MeSH
- vazba proteinů MeSH
- výpočetní biologie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
