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Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment

The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or “masked,” from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells. Previous r...

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Autores principales: Lin, Jia, Wester, Michael J., Graus, Matthew S., Lidke, Keith A., Neumann, Aaron K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791122/
https://www.ncbi.nlm.nih.gov/pubmed/26792838
http://dx.doi.org/10.1091/mbc.E15-06-0355
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author Lin, Jia
Wester, Michael J.
Graus, Matthew S.
Lidke, Keith A.
Neumann, Aaron K.
author_facet Lin, Jia
Wester, Michael J.
Graus, Matthew S.
Lidke, Keith A.
Neumann, Aaron K.
author_sort Lin, Jia
collection PubMed
description The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or “masked,” from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells. Previous research suggested that the physical presentation geometry of β-glucan might determine whether it can be recognized by Dectin-1. We used direct stochastic optical reconstruction microscopy to explore the fine structure of β-glucan exposed on C. albicans cell walls before and after treatment with the antimycotic drug caspofungin, which alters glucan exposure. Most surface-accessible glucan on C. albicans yeast and hyphae is limited to isolated Dectin-1–binding sites. Caspofungin-induced unmasking caused approximately fourfold to sevenfold increase in total glucan exposure, accompanied by increased phagocytosis efficiency of DCs for unmasked yeasts. Nanoscopic imaging of caspofungin-unmasked C. albicans cell walls revealed that the increase in glucan exposure is due to increased density of glucan exposures and increased multiglucan exposure sizes. These findings reveal that glucan exhibits significant nanostructure, which is a previously unknown physical component of the host–Candida interaction that might change during antifungal chemotherapy and affect innate immune activation.
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spelling pubmed-47911222016-05-30 Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment Lin, Jia Wester, Michael J. Graus, Matthew S. Lidke, Keith A. Neumann, Aaron K. Mol Biol Cell Articles The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or “masked,” from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells. Previous research suggested that the physical presentation geometry of β-glucan might determine whether it can be recognized by Dectin-1. We used direct stochastic optical reconstruction microscopy to explore the fine structure of β-glucan exposed on C. albicans cell walls before and after treatment with the antimycotic drug caspofungin, which alters glucan exposure. Most surface-accessible glucan on C. albicans yeast and hyphae is limited to isolated Dectin-1–binding sites. Caspofungin-induced unmasking caused approximately fourfold to sevenfold increase in total glucan exposure, accompanied by increased phagocytosis efficiency of DCs for unmasked yeasts. Nanoscopic imaging of caspofungin-unmasked C. albicans cell walls revealed that the increase in glucan exposure is due to increased density of glucan exposures and increased multiglucan exposure sizes. These findings reveal that glucan exhibits significant nanostructure, which is a previously unknown physical component of the host–Candida interaction that might change during antifungal chemotherapy and affect innate immune activation. The American Society for Cell Biology 2016-03-15 /pmc/articles/PMC4791122/ /pubmed/26792838 http://dx.doi.org/10.1091/mbc.E15-06-0355 Text en © 2016 Lin et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Lin, Jia
Wester, Michael J.
Graus, Matthew S.
Lidke, Keith A.
Neumann, Aaron K.
Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment
title Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment
title_full Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment
title_fullStr Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment
title_full_unstemmed Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment
title_short Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment
title_sort nanoscopic cell-wall architecture of an immunogenic ligand in candida albicans during antifungal drug treatment
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791122/
https://www.ncbi.nlm.nih.gov/pubmed/26792838
http://dx.doi.org/10.1091/mbc.E15-06-0355
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