'Omics' technologies have facilitated the identification of hundreds to thousands of tick molecules that mediate tick feeding and play a role in the transmission of tick-borne diseases. Deep sequencing methodologies have played a key role in this knowledge accumulation, profoundly facilitating the study of the biology of disease vectors lacking reference genomes. For example, the nucleotide sequences of the entire set of tick salivary effectors, the so-called tick 'sialome', now contain at least one order of magnitude more transcript sequences compared to similar projects based on Sanger sequencing. Tick feeding is a complex and dynamic process, and while the dynamic 'sialome' is thought to mediate tick feeding success, exactly how transcriptome dynamics relate to tick-host-pathogen interactions is still largely unknown. The identification and, importantly, the functional analysis of the tick 'sialome' is expected to shed light on this 'black box'. This information will be crucial for developing strategies to block pathogen transmission, not only for anti-tick vaccine development but also the discovery and development of new, pharmacologically active compounds for human diseases.

• MeSH
• genom fyziologie   MeSH
• interakce hostitele a patogenu MeSH
• klíšťata genetika   fyziologie   MeSH
• lidé MeSH
• proteomika * MeSH
• slinné žlázy fyziologie   MeSH
• transkriptom fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

AIMS: As the most abundant cell population in the blood, erythrocytes represent an attractive source of nutrients and a protective niche to a number of pathogens. Previously, we observed the attachment of the myxozoan parasite Sphaerospora molnari to erythrocytes of its host, common carp (Cyprinus carpio), raising a number of questions about the nature of this interaction. METHODS AND RESULTS: We elucidated the impact of S molnari on the number of erythrocytes in healthy and immunocompromised fish, over a period of 6 weeks. While we observed only a mild decrease in RBC numbers in healthy individuals, we witnessed gradual and finally severe haemolytic anaemia in immunosuppressed fish. Accompanying this overt loss was increased erythropoiesis as represented by an increase of erythroblasts in the blood. In vitro, we demonstrated the uptake of host proteins from CFSE-labelled erythrocytes, ultimately inducing death of host RBCs, likely for nutrient gain of the parasite. Nevertheless, the results do not exclude a possible role of erythrocyte-derived proteins in immune evasion. CONCLUSION: Overall, the obtained data provide first evidence for the previously unknown appetite of myxozoan parasites for host erythrocytes and create an important framework for future investigations into the molecular mechanisms underlining this interaction.

• MeSH
• erytrocyty parazitologie   MeSH
• erytropoéza fyziologie   MeSH
• fylogeneze MeSH
• hemolytické anemie parazitologie   MeSH
• kapři parazitologie   MeSH
• Myxozoa fyziologie   MeSH
• nemoci ryb parazitologie   MeSH
• stravovací zvyklosti fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Trichobilharzia regenti (Schistosomatidae) percutaneously infects birds and mammals and invades their central nervous system (CNS). Here, we characterized the peripheral immune response of infected mice and showed how it was influenced by the parasite-induced inflammation in the skin and the CNS. As revealed by flow cytometry, T cells expanded in the spleen and the CNS-draining lymph nodes 7-14 days post-infection. Both T-bet+ and GATA-3+ T cells were markedly elevated suggesting a mixed type 1/2 immune response. However, it dropped after 7 dpi most likely being unaffected by the neuroinflammation. Splenocytes from infected mice produced a high amount of IFN-γ and, to a lesser extent, IL-10, IL-4 and IL-17 after in vitro stimulation by cercarial homogenate. Nevertheless, it had only a limited capacity to alter the maturation status of bone marrow-derived dendritic cells (BMDCs), contrary to the recombinant T. regenti cathepsin B2, which also strongly augmented expression of Ccl5, Cxcl10, Il12a, Il33 and Il10 by BMDCs. Taken together, mice infected with T. regenti developed the mixed type 1/2 immune response, which was driven by the early skin inflammation rather than the late neuroinflammation. Parasite peptidases might play an active role in triggering the host immune response.

• MeSH
• cerkárie imunologie   MeSH
• cytokiny imunologie   MeSH
• dendritické buňky imunologie   MeSH
• dermatitida imunologie   parazitologie   patologie   MeSH
• infekce červy třídy Trematoda imunologie   parazitologie   MeSH
• kathepsin B metabolismus   MeSH
• kůže imunologie   parazitologie   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• Schistosomatidae imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• zánět parazitologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This study revises our understanding of the effectiveness of cell-mediated adaptive immunity and treatment against microsporidia using molecular detection and quantification of microsporidia in immunocompetent C57Bl/6 and immunodeficient CD4-/-and CD8-/-mice for the first time. We demonstrate an intense dissemination of microsporidia into most organs within the first weeks post-infection in all strains of mice, followed by a chronic infection characterized by microsporidia persistence in CD4-/-and C57Bl/6 mice and a lethal outcome for CD8-/-mice. Albendazole application reduces microsporidia burden in C57Bl/6 and CD4-/-mice, whereas CD8-/-mice experience only a temporary effect of the treatment. Surprisingly, treated CD8-/-mice survived the entire experimental duration despite enormous microsporidia burden. On the basis of our results, we conclude that microsporidia survive despite the presence of immune mechanisms and treatments that are currently considered to be effective and therefore that CD8 T lymphocytes represent a major, but not sole effector mechanism controlling microsporidiosis. Furthermore, the survival of mice does not correspond to spore burden, which provides new insight into latent microsporidiosis from an epidemiological point of view.

• MeSH
• adaptivní imunita imunologie   MeSH
• albendazol terapeutické užití   MeSH
• anthelmintika terapeutické užití   MeSH
• buněčná imunita imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• Encephalitozoon cuniculi růst a vývoj   imunologie   MeSH
• encephalitozoonóza imunologie   mikrobiologie   MeSH
• lymfopenie imunologie   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission.

• MeSH
• antigeny imunologie   MeSH
• infestace klíšťaty parazitologie   prevence a kontrola   MeSH
• interakce hostitele a patogenu MeSH
• klíšťata imunologie   MeSH
• lidé MeSH
• nemoci přenášené klíšťaty parazitologie   prevence a kontrola   MeSH
• vakcíny imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.

• MeSH
• chemokin CCL1 imunologie   MeSH
• chemokin CCL2 imunologie   MeSH
• chemokin CXCL2 imunologie   MeSH
• klíště imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• organismy bez specifických patogenů MeSH
• sliny imunologie   MeSH
• Th2 buňky imunologie   MeSH
• uvolňování histaminu MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-β mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-β. LPS-stimulated dendritic cells release IFN-β which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-β responses which may consequently increase the pathogen load after transmission via tick saliva.

• MeSH
• Borrelia burgdorferi fyziologie   MeSH
• cystatiny imunologie   MeSH
• dendritické buňky imunologie   MeSH
• fosforylace MeSH
• interferon beta imunologie   MeSH
• interferonový regulační faktor 7 imunologie   MeSH
• klíště imunologie   mikrobiologie   MeSH
• lipopolysacharidy imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• receptory cytokinové imunologie   MeSH
• receptory interferonů metabolismus   MeSH
• slinné cystatiny imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Dendritic cells are a sentinel in defending against pathogens and tick saliva facilitates transmission of tick-borne pathogens by modulating the host immune response. The maturation of dendritic cells is inhibited by tick saliva. To elucidate the mechanism of this inhibition, we tested the impact of Ixodes ricinus tick saliva on signalling pathways activated by Toll-like receptor (TLR-2) ligand and Borrelia afzelii in spleen dendritic cells. The activation of nuclear factor-κB (NF-κB) p65 and phosphatidylinositol-3 kinase (PI3K)/Akt pathways was decreased by tick saliva upon both TLR-2 and Borrelia stimulation. Among the mitogen-activated protein kinases (MAPK), the activation of extracellular matrix-regulated kinase (Erk1/2) was suppressed by tick saliva, but not p38. In response to spirochaetes, the amount of TNF-α decreased in the presence of tick saliva which was mediated by selective suppression of Erk1/2, NF-κB and Akt as tick saliva mimicked the effect of their specific inhibitors, UO126, IKK-IV and LY294002, respectively. Saliva-induced enhancement of IL-10 was not observed in the presence of specific inhibitor of Protein Kinase A (PKA), H-89, suggesting the involvement of PKA pathway in IL-10 production. Our cumulative data show that tick saliva interferes with several signalling pathways, thus modulating the immune functions of dendritic cells.

• MeSH
• 1-fosfatidylinositol-3-kinasa metabolismus   MeSH
• Borrelia burgdorferi komplex imunologie   MeSH
• dendritické buňky imunologie   MeSH
• imunologické faktory metabolismus   MeSH
• interleukin-10 sekrece   MeSH
• klíště patogenita   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• sliny metabolismus   MeSH
• TNF-alfa sekrece   MeSH
• toll-like receptor 2 imunologie   MeSH
• transkripční faktor RelA metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The role of CD4+ and CD8+ T lymphocytes in the development of a protective immune response against Cryptosporidium muris infection was studied by the reconstitution of severe combined immunodeficient (SCID) mice with well-defined populations of either naive or immune CD8+ or CD4+ T lymphocytes. Adoptive transfer of both naive and immune CD4+ T lymphocyte subpopulations protects SCID mice against cryptosporidiosis. Moreover, a significant biological impact of activated CD8+ T cells against gastric cryptosporidiosis was observed. The significant difference in the course and intensity of the infection in reconstituted SCID mice was found to be dependent on the protective function of both the CD4+ and CD8+ T-cell populations transferred. While SCID mice reconstituted with either immune or naive CD4+ or immune CD8+ T-cell subpopulations resolved the infection within 29, 37 and 51 days post-infection, respectively, those reconstituted with naive CD8+ T cells suffered from chronic infection similar to control SCID mice. Reconstitution with CD4+ T cells resulted in suppression of oocyst excretion and shortening of patent period in comparison with SCID mice reconstituted with CD8+ T cells. Thus, although CD4+ T cells are considered important in protective immunity, our results are the first to demonstrate the involvement of activated CD8+ T lymphocytes in the protection of mice against gastric cryptosporidiosis.

• MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• Cryptosporidium imunologie   MeSH
• kryptosporidióza imunologie   MeSH
• myši SCID MeSH
• myši MeSH
• převzatá imunita MeSH
• žaludek imunologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH