tick saliva Dotaz Zobrazit nápovědu
Tick-borne encephalitis virus is an important human pathogen, naturally delivered into host skin via a tick bite. To examine the effects of the virus on dendritic cell biology, we cultured dendritic cells with two tick-borne encephalitis virus strains of different virulence in the presence of Ixodes ricinus tick saliva. Tick saliva treatment increased proportion of virus-infected cells, led to a decrease in virus-induced TNF-alpha and IL-6 production and to reduced virus-induced apoptosis. Our data indicate that tick saliva modulate virus-mediated alterations in dendritic cells, thus probably being involved in the early infection process in the host.
- MeSH
- dendritické buňky virologie MeSH
- interleukin-6 metabolismus MeSH
- klíště virologie MeSH
- kultivované buňky MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- sliny fyziologie MeSH
- TNF-alfa metabolismus MeSH
- viry klíšťové encefalitidy patogenita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- 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
Tick-borne diseases pose a global medical problem. As transmission of tick-borne pathogens to their hosts occurs during tick feeding, development of vaccines thwarting this process could potentially prevent transmission of multiple tick-borne pathogens. The idea of tick vaccines is based on the phenomenon of acquired tick immunity, rejection of ticks feeding on hosts which were repeatedly infested by ticks. Recently, we demonstrated that saliva of the blacklegged tick Ixodes scapularis, which is the main vector of tick-borne pathogens in northeast USA, is sufficient for induction of tick immunity in the guinea pig model and that immunity directed against tick glycoproteins is important in this phenomenon. Nevertheless, immunity elicited against individual tick salivary antigens, which have been identified and tested so far, provided only modest tick rejection. We therefore now tested fractions of tick saliva produced by liquid chromatography for their ability to induce tick immunity in the guinea pig model. Immunization with all individual fractions elicited antibodies that reacted with tick saliva, however only some fractions displayed the ability to induce robust protective tick immunity. Mass spectrometry analysis led to identification of 24 proteins present only in saliva fractions which were able to induce tick immunity, suggesting suitable candidates for development of a tick vaccine.
- MeSH
- chromatografie kapalinová MeSH
- glykoproteiny MeSH
- klíště * MeSH
- morčata MeSH
- sliny MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Tumour necrosis factor (TNF) plays a central role in the inflammatory process. In the skin, it contributes to immune containment of tick-transmitted pathogens like Borrelia burgdorferi. In the saliva of some tick species, active compounds are present that inhibit detection of TNF in specific ELISA. We compared the presence of anti-TNF activity in saliva or salivary gland extract from 11 tick species from the family Ixodidae and demonstrated it in genera Ixodes Latreille, 1795 and Haemaphysalis Koch, 1844. Analysis of anti-TNF activity in Ixodes ricinus (Linnaeus, 1758) saliva during the feeding period showed that it is present in the late, rapid phase of engorgement. Significance of anti-TNF activity for tick feeding and transmission of tick-borne pathogens is discussed.
- MeSH
- klíště * MeSH
- sliny * imunologie MeSH
- stravovací zvyklosti MeSH
- TNF-alfa * antagonisté a inhibitory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Type I interferons (IFN-α and IFN-β) are crucial determinants of the host immune response and tick saliva modulates this response, thus facilitating the transmission of tickborne pathogens. The current study therefore examines the effect of Ixodes ricinus tick saliva on IFN-β signalling in murine dendritic cells using lipopolysaccharide (LPS) and Borrelia afzelii spirochaetes as inducers. Activated dendritic cells secret IFN that activates Signal Transducer and Activator of Transcription 1 (STAT-1). Our results show that Borrelia-induced activation of STAT-1 was suppressed by tick saliva. As the amount of secreted IFN-β was not influenced by tick saliva, the results indicated that saliva affected the interferon pathway at the IFN receptor or downstream of it. By using recombinant IFN-β, we show that tick saliva attenuates IFN-triggered STAT-1 activation. Tick saliva also inhibited LPS-induced IFN-β production suggesting that saliva interferes with the activation of the pathway that mediates IFN-β induction. Our data indicate that I. ricinus tick saliva may modulate the host immune response by attenuating the initial signal transduction pathway of type I IFN.
- MeSH
- Borrelia burgdorferi komplex patogenita MeSH
- dendritické buňky imunologie MeSH
- imunologické faktory imunologie metabolismus MeSH
- interferon typ I antagonisté a inhibitory imunologie MeSH
- klíště imunologie MeSH
- kultivované buňky MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- sliny imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Interaction between mouse dendritic cells (DCs) and Borrelia afzelii spirochetes was monitored on three different levels: phagocytosis of spirochetes by DCs, production of cytokines by Borrelia-stimulated DCs and the ability of Borrelia-exposed DCs to activate specific CD4+ T lymphocytes. The effect of Ixodes ricinus tick saliva on each of these interactions was examined. Tick saliva was shown to decrease the number of phagocytosing DCs. The ability of Borrelia-exposed DCs to induce both proliferation and IL-2 production by specific CD4+ T cells was significantly reduced by tick saliva. And surprisingly, we have shown an inhibitory effect of tick saliva on the production of both Th1 (TNF-α and IL-6) and Th2 (IL-10) cytokines by DCs. Our data reveal a complex inhibitory effect of tick saliva on Borrelia-DCs interaction.
- MeSH
- aktivace lymfocytů MeSH
- Borrelia burgdorferi komplex imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- cytokiny sekrece MeSH
- dendritické buňky imunologie MeSH
- fagocytóza MeSH
- imunologické faktory imunologie MeSH
- klíště mikrobiologie MeSH
- myši inbrední C3H MeSH
- myši MeSH
- sliny imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Introduction: We developed a new simple method to assess the composition of proteinaceous components in the saliva of Ornithodoros moubata, the main vehicle for pathogen transmission and a likely source of bioactive molecules acting at the tick-vertebrate host interface. To collect naturally expectorated saliva from the ticks we employed an artificial membrane feeding technique using a simple, chemically defined diet containing phagostimulants and submitted native saliva samples collected in this way for liquid chromatography-mass spectrometry (LC-MS) analysis. These experiments were conducted with groups of uninfected ticks as well as with O. moubata infected with B. duttonii. The ticks exhibited a fair feeding response to the tested diet with engorgement rates reaching as high as 60-100% of ticks per feeding chamber. The LC-MS analysis identified a total of 17 and 15 proteins in saliva samples from the uninfected and infected O. moubata nymphs, respectively. Importantly, the analysis was sensitive enough to detect up to 9 different proteins in the samples of saliva containing diet upon which as few as 6 nymphal ticks fed during the experiments. Some of the proteins recognized in the analysis are well known for their immunomodulatory activity in a vertebrate host, whereas others are primarily thought of as structural or "housekeeping" proteins and their finding in the naturally expectorated tick saliva confirms that they can be secreted and might serve some functions at the tick-host interface. Most notably, some of the proteins that have long been suspected for their importance in the vector-pathogen interactions of Borrelia spirochetes were detected only in the samples from infected ticks, suggesting that their expression was altered by the persistent colonization of the tick's salivary glands by spirochetes. The simple method described herein is an important addition to the toolbox available to study the vector-host-pathogen interactions in the rapidly feeding soft ticks.
- MeSH
- Argasidae * MeSH
- Borrelia * fyziologie MeSH
- Ornithodoros * MeSH
- sliny MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Similarly to other blood-feeding arthropods, ticks have evolved immunosuppressive mechanisms enabling them to overcome the host immune system. Although the immunomodulatory effect of tick saliva on several cell populations of the immune system has been extensively studied, little is known about its impact on dendritic cells (DCs). We have examined the effect of Ixodes ricinus tick saliva on DC function in vitro and in vivo. Exposure of DCs to tick saliva in vitro resulted in impaired maturation, upon CD40 or TLR9, TLR3 and TLR7 ligation, as well as reduced Ag presentation capacity. Administration of tick saliva in vivo significantly inhibited maturation and early migration of DCs from inflamed skin to draining lymph nodes, and decreased the capacity of lymph node DCs to present soluble Ag to specific T cells. Moreover, saliva-exposed DCs failed to induce efficient Th1 and Th17 polarization and promoted development of Th2 responses. Our data reveal a complex inhibitory effect exerted by tick saliva on DC function. Given the role of DCs as the key instigators of adaptive immune responses, alteration of their function might represent a major mechanism of tick-mediated immune evasion.
- MeSH
- antigeny CD40 imunologie MeSH
- dendritické buňky imunologie MeSH
- financování organizované MeSH
- imunologická tolerance imunologie MeSH
- klíště imunologie MeSH
- lymfatické uzliny imunologie MeSH
- myši MeSH
- pohyb buněk imunologie MeSH
- prezentace antigenu imunologie MeSH
- sliny imunologie MeSH
- Th1 buňky imunologie MeSH
- Th2 buňky imunologie MeSH
- toll-like receptory imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
Ixodes ricinus tick saliva-activated transmission of Borrelia burgdorferi sensu stricto spirochetes was studied on the C3H/HeN mouse model. The influence of the feeding of uninfected nymphs on the proliferation and distribution of intradermally inoculated spirochetes was compared with the effect of co-inoculated saliva or salivary gland extract (SGE), respectively. Spirochete loads in murine tissues were evaluated using real-time q-PCR. SGE induced significantly increased spirochete numbers in the skin on the days 4 and 6 post-infection (p.i.). On the other hand, decreased bacterial load in the heart of SGE-treated mice was demonstrated in comparison with control animals. The inoculation of tick saliva increased spirochete load in the urinary bladder on day 6 p.i., while the number of spirochetes in the heart declined on day 6 p.i. The feeding of I. ricinus nymphs raised the spirochete load in the bladder on the days 4 and 6 p.i. On day 6, the number of spirochetes found in the heart was significantly lower than in controls. The prevalence of spirochetes in ticks infected by feeding on mice was more than 10 times higher when the mice were infected with the mixture of spirochetes and saliva or SGE, in comparison with spirochetes alone. The presence of SGE in the infectious inoculum increased the spirochete burden per tick from 0 to almost 28,000. Taken together, these results show a very early effect of tick saliva on the proliferation and distribution of Borrelia spirochetes in the host, probably due to the effect of saliva on the host innate immunity mechanisms.
- MeSH
- Borrelia burgdorferi růst a vývoj MeSH
- klíště mikrobiologie MeSH
- kůže mikrobiologie MeSH
- lymeská nemoc mikrobiologie přenos veterinární MeSH
- močový měchýř mikrobiologie MeSH
- myši inbrední C3H MeSH
- myši MeSH
- počet mikrobiálních kolonií MeSH
- sliny mikrobiologie MeSH
- srdce mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
