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The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan

Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fum...

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Autores principales: Reedy, Jennifer L., Crossen, Arianne J., Negoro, Paige E., Harding, Hannah Brown, Ward, Rebecca A., Vargas-Blanco, Diego A., Timmer, Kyle D., Reardon, Christopher M., Basham, Kyle J., Mansour, Michael K., Wüthrich, Marcel, Fontaine, Thierry, Latgé, Jean-Paul, Vyas, Jatin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973300/
https://www.ncbi.nlm.nih.gov/pubmed/36598192
http://dx.doi.org/10.1128/mbio.03184-22
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author Reedy, Jennifer L.
Crossen, Arianne J.
Negoro, Paige E.
Harding, Hannah Brown
Ward, Rebecca A.
Vargas-Blanco, Diego A.
Timmer, Kyle D.
Reardon, Christopher M.
Basham, Kyle J.
Mansour, Michael K.
Wüthrich, Marcel
Fontaine, Thierry
Latgé, Jean-Paul
Vyas, Jatin M.
author_facet Reedy, Jennifer L.
Crossen, Arianne J.
Negoro, Paige E.
Harding, Hannah Brown
Ward, Rebecca A.
Vargas-Blanco, Diego A.
Timmer, Kyle D.
Reardon, Christopher M.
Basham, Kyle J.
Mansour, Michael K.
Wüthrich, Marcel
Fontaine, Thierry
Latgé, Jean-Paul
Vyas, Jatin M.
author_sort Reedy, Jennifer L.
collection PubMed
description Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2-dependent signaling, including activation of spleen tyrosine kinase, gene transcription, and tumor necrosis factor alpha (TNF-α) production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan, which leads to a proinflammatory immune response in the lung.
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spelling pubmed-99733002023-03-01 The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan Reedy, Jennifer L. Crossen, Arianne J. Negoro, Paige E. Harding, Hannah Brown Ward, Rebecca A. Vargas-Blanco, Diego A. Timmer, Kyle D. Reardon, Christopher M. Basham, Kyle J. Mansour, Michael K. Wüthrich, Marcel Fontaine, Thierry Latgé, Jean-Paul Vyas, Jatin M. mBio Research Article Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2-dependent signaling, including activation of spleen tyrosine kinase, gene transcription, and tumor necrosis factor alpha (TNF-α) production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan, which leads to a proinflammatory immune response in the lung. American Society for Microbiology 2023-01-04 /pmc/articles/PMC9973300/ /pubmed/36598192 http://dx.doi.org/10.1128/mbio.03184-22 Text en Copyright © 2023 Reedy et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Reedy, Jennifer L.
Crossen, Arianne J.
Negoro, Paige E.
Harding, Hannah Brown
Ward, Rebecca A.
Vargas-Blanco, Diego A.
Timmer, Kyle D.
Reardon, Christopher M.
Basham, Kyle J.
Mansour, Michael K.
Wüthrich, Marcel
Fontaine, Thierry
Latgé, Jean-Paul
Vyas, Jatin M.
The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan
title The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan
title_full The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan
title_fullStr The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan
title_full_unstemmed The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan
title_short The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan
title_sort c-type lectin receptor dectin-2 is a receptor for aspergillus fumigatus galactomannan
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973300/
https://www.ncbi.nlm.nih.gov/pubmed/36598192
http://dx.doi.org/10.1128/mbio.03184-22
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