Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection
Abstract Candida albicans is the most common human fungal pathogen, causing diseases ranging from local to life-threating systemic infections. Tyrosine kinase 2 (TYK2), a crucial mediator in several cytokine signaling pathways, has been associated with protective functions in various microbial infec...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54888-6 |
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| _version_ | 1846137026581102592 |
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| author | Sara Miranda Caroline Lassnig Kristina Schmidhofer Hrönn Kjartansdottir Claus Vogl Simone Tangermann Irina Tsymala Verena Babl Mathias Müller Karl Kuchler Birgit Strobl |
| author_facet | Sara Miranda Caroline Lassnig Kristina Schmidhofer Hrönn Kjartansdottir Claus Vogl Simone Tangermann Irina Tsymala Verena Babl Mathias Müller Karl Kuchler Birgit Strobl |
| author_sort | Sara Miranda |
| collection | DOAJ |
| description | Abstract Candida albicans is the most common human fungal pathogen, causing diseases ranging from local to life-threating systemic infections. Tyrosine kinase 2 (TYK2), a crucial mediator in several cytokine signaling pathways, has been associated with protective functions in various microbial infections. However, its specific contribution in the immune response to fungal infections has remained elusive. In this study, we show that mice lacking TYK2 or its enzymatic activity exhibit enhanced resistance to C. albicans skin infections, limiting fungal spread and accelerating wound healing. Impaired TYK2-signaling prompted the formation of a distinctive layer of necrotic neutrophils around the fungal pathogens. Transcriptomic analysis revealed TYK2’s pivotal role in regulating interferon-inducible genes in neutrophils, thereby impacting their antifungal capacity during infection. Furthermore, we show that TYK2-dependent interferon-gamma (IFNγ) production contributes to fungal dissemination from the skin to the kidneys. Our study uncovers a hitherto unrecognized detrimental role of TYK2 in cutaneous C. albicans infections. |
| format | Article |
| id | doaj-art-fbf19051b7cf49bba81b934693ebfa2a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-fbf19051b7cf49bba81b934693ebfa2a2024-12-08T12:35:06ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-54888-6Lack of TYK2 signaling enhances host resistance to Candida albicans skin infectionSara Miranda0Caroline Lassnig1Kristina Schmidhofer2Hrönn Kjartansdottir3Claus Vogl4Simone Tangermann5Irina Tsymala6Verena Babl7Mathias Müller8Karl Kuchler9Birgit Strobl10Centre of Biological Sciences, University of Veterinary Medicine ViennaCentre of Biological Sciences, University of Veterinary Medicine ViennaCentre of Biological Sciences, University of Veterinary Medicine ViennaCentre of Biological Sciences, University of Veterinary Medicine ViennaCentre of Biological Sciences, University of Veterinary Medicine ViennaCentre of Pathobiology, University of Veterinary Medicine ViennaMax Perutz Labs, Vienna Biocenter Campus (VBC)Centre of Biological Sciences, University of Veterinary Medicine ViennaCentre of Biological Sciences, University of Veterinary Medicine ViennaMax Perutz Labs, Vienna Biocenter Campus (VBC)Centre of Biological Sciences, University of Veterinary Medicine ViennaAbstract Candida albicans is the most common human fungal pathogen, causing diseases ranging from local to life-threating systemic infections. Tyrosine kinase 2 (TYK2), a crucial mediator in several cytokine signaling pathways, has been associated with protective functions in various microbial infections. However, its specific contribution in the immune response to fungal infections has remained elusive. In this study, we show that mice lacking TYK2 or its enzymatic activity exhibit enhanced resistance to C. albicans skin infections, limiting fungal spread and accelerating wound healing. Impaired TYK2-signaling prompted the formation of a distinctive layer of necrotic neutrophils around the fungal pathogens. Transcriptomic analysis revealed TYK2’s pivotal role in regulating interferon-inducible genes in neutrophils, thereby impacting their antifungal capacity during infection. Furthermore, we show that TYK2-dependent interferon-gamma (IFNγ) production contributes to fungal dissemination from the skin to the kidneys. Our study uncovers a hitherto unrecognized detrimental role of TYK2 in cutaneous C. albicans infections.https://doi.org/10.1038/s41467-024-54888-6 |
| spellingShingle | Sara Miranda Caroline Lassnig Kristina Schmidhofer Hrönn Kjartansdottir Claus Vogl Simone Tangermann Irina Tsymala Verena Babl Mathias Müller Karl Kuchler Birgit Strobl Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection Nature Communications |
| title | Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection |
| title_full | Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection |
| title_fullStr | Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection |
| title_full_unstemmed | Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection |
| title_short | Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection |
| title_sort | lack of tyk2 signaling enhances host resistance to candida albicans skin infection |
| url | https://doi.org/10.1038/s41467-024-54888-6 |
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