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4. CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV.

Author

Immler, Roland, Nussbaumer, Katrin, Doerner, Axel, El Bounkari, Omar, Huber, Silke, Abisch, Janine, Napoli, Matteo, Schmidt, Sarah, Margraf, Andreas, Pruenster, Monika, Rohwedder, Ina, Lange-Sperandio, Baerbel, Mall, Marcus A., de Jong, Renske, Ohnmacht, Caspar, Bernhagen, Juergen, Voehringer, David, Marth, Jamey D., Frommhold, David, and Sperandio, Markus

Subjects
EOSINOPHILS, HOMEOSTASIS, PERITONEUM, ALLERGIES, ADIPOSE tissues
Abstract

Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase St3gal4-/- mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of St3gal4-/- mice. Ex vivo flow chamber assays uncovered reduced adhesion of St3gal4-/- compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to St3gal4-/- eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from St3gal4-/- eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated St3gal4-/- eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in St3gal4-deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Detection of Cleaved Stx2a in the Blood of STEC-Infected Patients

Author

Varrone, Elisa, primary, Carnicelli, Domenica, additional, He, Xiaohua, additional, Grasse, Marco, additional, Stampfer, Karin, additional, Huber, Silke, additional, Kellnerová, Sára, additional, Tazzari, Pier Luigi, additional, Ricci, Francesca, additional, Paterini, Paola, additional, Ardissino, Gianluigi, additional, Morabito, Stefano, additional, Orth-Höller, Dorothea, additional, Würzner, Reinhard, additional, and Brigotti, Maurizio, additional

Published
2023
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7. Enzymatic Cleavage of Stx2a in the Gut and Identification of Pancreatic Elastase and Trypsin as Possible Main Cleavers

Author

Kellnerová, Sára, primary, Huber, Silke, additional, Massri, Mariam, additional, Fleischer, Verena, additional, Losso, Klemens, additional, Sarg, Bettina, additional, Kremser, Leopold, additional, Talasz, Heribert, additional, He, Xiaohua, additional, Varrone, Elisa, additional, Brigotti, Maurizio, additional, Ardissino, Gianluigi, additional, Orth-Höller, Dorothea, additional, and Würzner, Reinhard, additional

Published
2023
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9. Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients

Author

Eichhorn, Tanja, primary, Huber, Silke, additional, Weiss, René, additional, Ebeyer-Masotta, Marie, additional, Lauková, Lucia, additional, Emprechtinger, Robert, additional, Bellmann-Weiler, Rosa, additional, Lorenz, Ingo, additional, Martini, Judith, additional, Pirklbauer, Markus, additional, Orth-Höller, Dorothea, additional, Würzner, Reinhard, additional, and Weber, Viktoria, additional

Published
2023
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14. Influence of Glucose on Candida albicans and the Relevance of the Complement FH-Binding Molecule Hgt1 in a Murine Model of Candidiasis

Author

Harpf, Verena, Kenno, Samyr, Rambach, Günter, Fleischer, Verena, Parth, Nadia, Weichenberger, Christian X, Garred, Peter, Huber, Silke, Lass-Flörl, Cornelia, Speth, Cornelia, Würzner, Reinhard, Harpf, Verena, Kenno, Samyr, Rambach, Günter, Fleischer, Verena, Parth, Nadia, Weichenberger, Christian X, Garred, Peter, Huber, Silke, Lass-Flörl, Cornelia, Speth, Cornelia, and Würzner, Reinhard

Abstract

Candidiasis is common in diabetic patients. Complement evasion is facilitated by binding complement factor H (FH). Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans. Euglycemic and diabetic mice were intravenously challenged with either Candida albicans lacking Hgt1 (hgt1-/-) or its parental strain (SN152). Survival and clinical status were monitored over 14 days. In vitro, Candida albicans strains were grown at different glucose concentrations, opsonized with human serum, and checked for C3b/iC3b and FH deposition. Phagocytosis was studied by fluorescein isothiocyanate-labeled opsonized yeast cells incubated with granulocytes. The murine model demonstrated a significantly higher virulence of SN152 in diabetic mice and an overall increased lethality of mice challenged with hgt1-/-. In vitro lower phagocytosis and C3b/iC3b deposition and higher FH deposition were demonstrated for SN152 incubated at higher glucose concentrations, while there was no difference on hgt1-/-at physiological glucose concentrations. Despite C3b/iC3b and FH deposition being glucose-dependent, this effect has a minor influence on phagocytosis. The absence of Hgt1 is diminishing this dependency on complement deposition, but it cannot be attributed to being beneficial in a murine model.

Published
2022

15. Influence of Glucose on Candida albicans and the Relevance of the Complement FH-Binding Molecule Hgt1 in a Murine Model of Candidiasis

Author

Harpf, Verena, primary, Kenno, Samyr, additional, Rambach, Günter, additional, Fleischer, Verena, additional, Parth, Nadia, additional, Weichenberger, Christian X., additional, Garred, Peter, additional, Huber, Silke, additional, Lass-Flörl, Cornelia, additional, Speth, Cornelia, additional, and Würzner, Reinhard, additional

Published
2022
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16. Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections

Author

Huber, Silke, primary, Massri, Mariam, additional, Grasse, Marco, additional, Fleischer, Verena, additional, Kellnerová, Sára, additional, Harpf, Verena, additional, Knabl, Ludwig, additional, Heiner, Tatjana, additional, Kummann, Moritz, additional, Neurauter, Magdalena, additional, Rambach, Günter, additional, Speth, Cornelia, additional, and Würzner, Reinhard, additional

Published
2021
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17. Regimen of Coronavirus Disease 2019 Vaccination Influences Extent and Kinetics of Antibody Avidity.

Author

Rössler, Annika, Kimpel, Janine, Fleischer, Verena, Huber, Silke, Laer, Dorothee von, Borena, Wegene, Würzner, Reinhard, Group, the HEVACC Study, von Laer, Dorothee, and HEVACC Study Group

Subjects
COVID-19, VACCINATION, ANTIBODY titer, ADENOVIRUS diseases, IMMUNOGLOBULINS, CORONAVIRUS diseases
Abstract

We investigated antibody titers and avidity after heterologous versus homologous coronavirus disease 2019 vaccination over 6 months after the second dose. We found a significantly higher avidity in regimens including at least 1 dose of the adenoviral vector vaccine ChAdOx1-S compared with 2 doses of the mRNA vaccine BNT162b2. [ABSTRACT FROM AUTHOR]

Published
2022
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19. Culture-Free Detection of Antibiotic Resistance Markers from Native Patient Samples by Hybridization Capture Sequencing

Author

Ferreira, Ines, primary, Lepuschitz, Sarah, additional, Beisken, Stephan, additional, Fiume, Giuseppe, additional, Mrazek, Katharina, additional, Frank, Bernhard J. H., additional, Huber, Silke, additional, Knoll, Miriam A., additional, von Haeseler, Arndt, additional, Materna, Arne, additional, Hofstaetter, Jochen G., additional, Posch, Andreas E., additional, and Weinberger, Johannes, additional

Published
2021
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20. Genomic and Phenotypic Analysis of Linezolid-Resistant Staphylococcus epidermidis in a Tertiary Hospital in Innsbruck, Austria

Author

Huber, Silke, primary, Knoll, Miriam A., additional, Berktold, Michael, additional, Würzner, Reinhard, additional, Brindlmayer, Anita, additional, Weber, Viktoria, additional, Posch, Andreas E., additional, Mrazek, Katharina, additional, Lepuschitz, Sarah, additional, Ante, Michael, additional, Beisken, Stephan, additional, Orth-Höller, Dorothea, additional, and Weinberger, Johannes, additional

Published
2021
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21. Die Macht des Wortes! Die persuasive Funktion politischer (Wahlkampf-)Kommunikation. Darstellungspolitik als wesentlicher Bestandteil politischer Partizipation

Author

Huber, Silke

Abstract

Die Politik ist das Wesen eines jeden Landes. Obgleich sie als solches regelmäßig als Sündenbock für etwaige wirtschaftliche oder soziale Verfehlungen herhalten muss oder oftmals aus anderen Gründen - mal zu Recht, mal ungerechtfertigt - gerne an den moralischen Pranger gestellt wird, bildet sie „als Wesen eines jeden Landes“ dennoch einen wichtigen Bestandteil unseres Zusammenlebens. Gleichermaßen verhält es sich mit dem politischen Sprachgebrauch in der Öffentlichkeit bzw. der Darstellungspolitik im Allgemeinen. So stellt die politische Sprache nicht nur ein akzidentelles Instrument der Politik dar, sondern bildet sie primär die Bedingung ihrer Möglichkeiten. In diesem Sinne erscheint es, trotz der ständigen Konfrontation mit politischen Sprachprozessen sowohl in den Printmedien als auch im Fernsehen, nahezu unerklärlich, wie wenig Verständnis und Aufmerksamkeit diesem Thema seitens zahlreicher Wahlberechtiger und somit politischer Mitgestalter doch entgegen-gebracht wird. Besonders treffend formulierte es einst Erhard Eppler, deutscher Politiker der SPD, indem er meinte, dass sich in der Politik nur schwer zwischen Reden und Handeln unterscheiden lasse. Der Versuch, die politische Sprache einer engen oder weit definierten Fachsprache zuzuordnen, erweist sich aufgrund ihrer enormen Komplexität nahezu als impraktikabel und kann mitunter zu Identitäts- und Abgrenzungsprobleme führen Diesem Gedanke zugrundeliegend ergaben sich für die vorliegende Diplomarbeit nun folgende Fragen: Welcher sprachliche Methoden bedienen sich Politiker, um in der Öffentlichkeit zu überzeugen? Was zeichnet politisches Sprechverhalten aus? Welcher Terminologie bedienen sich Politiker, um den Wähler zu überzeugen? Wie lässt sich der politische Sprachgebrauch überhaupt definieren? Wie wirken Wahlplakate - basierend auf ihrer sprachlichen Gestaltung - auf den Wähler? Welcher Eindruck wird vermittelt? Welche politischen Strategien bzw. Ziele werden damit verfolgt? Lassen sich hinsichtlich ihrer sprachlichen Gestaltung Unterschiede, Gegensätze oder gar Übereinstimmungen feststellen? Hebt sich eine Partei bei ihrer Wahlwerbung besonders ab?

Published
2016
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22. Phänotypische und funktionelle Charakterisierung von Makrophagen während einer Typ-2 Immunantwort

Author

Huber, Silke, Haller, Dirk (Prof. Dr.), and Vöhringer, David (Prof. Dr.)

Subjects
Macrophagen, PD-L2, Naturwissenschaften, Makrophages, PD-L2, ddc:500
Abstract

Alternatively activated macrophages (AAM) differentiate through IL-4/IL-13-mediated activation of Stat6. Microarrays revealed that Stat6 is required for IL-4-induced up-regulation of PD-L2 in murine macrophages. Blockade of PD-L2 prevented the inhibitory activity of AAM against T cells. Retroviral transduction of PD-L2 into Stat6-deficient macrophages was sufficient to inhibit T cell proliferation. These results demonstrate that AAM inhibit T cells by Stat6-dependent expression of PD-L2. Alternativ aktivierte Makrophagen (AAM) differenzieren durch IL-4/IL-13-vermittelte Aktivierung von Stat6. Microarrays zeigten, dass PD-L2 durch IL-4 in murinen Makrophagen Stat6-abhängig induziert wird. Durch Blockierung von PD-L2 wurde die AAM-vermittelte Inhibierung von T-Zellen aufgehoben. Eine retrovirale Transduktion von PD-L2 in Stat6-defiziente Makrophagen war ausreichend, um T-Zellen zu inhibieren. Die Ergebnisse zeigen, dass AAM T-Zellen durch Expression von PD-L2 hemmen.

Published
2011

23. Phenotypic and functional characterization of macrophages during type 2 immune responses

Author

Haller, Dirk (Prof. Dr.), Vöhringer, David (Prof. Dr.), Huber, Silke, Haller, Dirk (Prof. Dr.), Vöhringer, David (Prof. Dr.), and Huber, Silke

Abstract

Alternatively activated macrophages (AAM) differentiate through IL-4/IL-13-mediated activation of Stat6. Microarrays revealed that Stat6 is required for IL-4-induced up-regulation of PD-L2 in murine macrophages. Blockade of PD-L2 prevented the inhibitory activity of AAM against T cells. Retroviral transduction of PD-L2 into Stat6-deficient macrophages was sufficient to inhibit T cell proliferation. These results demonstrate that AAM inhibit T cells by Stat6-dependent expression of PD-L2., Alternativ aktivierte Makrophagen (AAM) differenzieren durch IL-4/IL-13-vermittelte Aktivierung von Stat6. Microarrays zeigten, dass PD-L2 durch IL-4 in murinen Makrophagen Stat6-abhängig induziert wird. Durch Blockierung von PD-L2 wurde die AAM-vermittelte Inhibierung von T-Zellen aufgehoben. Eine retrovirale Transduktion von PD-L2 in Stat6-defiziente Makrophagen war ausreichend, um T-Zellen zu inhibieren. Die Ergebnisse zeigen, dass AAM T-Zellen durch Expression von PD-L2 hemmen.

Published
2011

27. Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB–induced Bcl-xLfor inhibition of apoptosis

Author

Schwartz, Christian, Willebrand, Ralf, Huber, Silke, Rupec, Rudolf A., Wu, Davina, Locksley, Richard, and Voehringer, David

Abstract

Eosinophils are associated with type 2 immune responses to allergens and helminths. They release various proinflammatory mediators and toxic proteins on activation and are therefore considered proinflammatory effector cells. Eosinophilia is promoted by the cytokines interleukin (IL)-3, IL-5, and granulocyte macrophage–colony-stimulating factor (GM-CSF) and can result from enhanced de novo production or reduced apoptosis. In this study, we show that only IL-5 induces differentiation of eosinophils from bone marrow precursors, whereas IL-5, GM-CSF, and to a lesser extent IL-3 promote survival of mature eosinophils. The receptors for these cytokines use the common β chain, which serves as the main signaling unit linked to signal transducer and activator of transcription 5, p38 mitogen-activated protein kinase, and nuclear factor (NF)-κB pathways. Inhibition of NF-κB induced apoptosis of in vitro cultured eosinophils. Selective deletion of IκBα in vivo resulted in enhanced expression of Bcl-xLand reduced apoptosis during helminth infection. Retroviral overexpression of Bcl-xLpromoted survival, whereas pharmacologic inhibition of Bcl-xLin murine or human eosinophils induced rapid apoptosis. These results suggest that therapeutic strategies targeting Bcl-xLin eosinophils could improve health conditions in allergic inflammatory diseases.

Published
2015
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28. Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apoptosis.

Author

Schwartz, Christian, Willebrand, Ralf, Huber, Silke, Rupec, Rudolf A., Davina Wu, Locksley, Richard, and Voehringer, David

Subjects
*EOSINOPHILS, *MICE, *PROTEIN kinases, *IMMUNOLOGY, *CYTOKINES, *APOPTOSIS
Abstract

Eosinophils are associated with type 2 immune responses to allergens and helminths. They release various proinflammatory mediators and toxic proteins on activation and are therefore considered proinflammatory effector cells. Eosinophilia is promoted by the cytokines interleukin (IL)-3, IL-5, and granulocyte macrophage-colony-stimulating factor (GM-CSF) and can result from enhanced de novo production or reduced apoptosis. In this study, we show that only IL-5 induces differentiation of eosinophils from bone marrow precursors, whereas IL-5, GM-CSF, and to a lesser extent IL-3 promote survival of mature eosinophils. The receptors for these cytokines use the common β chain, which serves as the main signaling unit linked to signal transducer and activator of transcription 5, p38 mitogen-activated protein kinase, and nuclear factor (NF)-κB pathways. Inhibition of NF-κB induced apoptosis of in vitro cultured eosinophils. Selective deletion of IκBα in vivo resulted in enhanced expression of Bcl-xL and reduced apoptosis during helminth infection. Retroviral overexpression of Bcl-xL promoted survival, whereas pharmacologic inhibition of Bcl-xL in murine or human eosinophils induced rapid apoptosis. These results suggest that therapeutic strategies targeting Bcl-xL in eosinophils could improve health conditions in allergic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Published
2015
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