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Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement
The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR....
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048669/ https://www.ncbi.nlm.nih.gov/pubmed/21205820 http://dx.doi.org/10.1074/jbc.M110.185025 |
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author | Gazi, Umut Rosas, Marcela Singh, Sonali Heinsbroek, Sigrid Haq, Imran Johnson, Simon Brown, Gordon D. Williams, David L. Taylor, Philip R. Martinez-Pomares, Luisa |
author_facet | Gazi, Umut Rosas, Marcela Singh, Sonali Heinsbroek, Sigrid Haq, Imran Johnson, Simon Brown, Gordon D. Williams, David L. Taylor, Philip R. Martinez-Pomares, Luisa |
author_sort | Gazi, Umut |
collection | PubMed |
description | The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through β-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate β-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and β-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection. |
format | Text |
id | pubmed-3048669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30486692011-03-08 Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement Gazi, Umut Rosas, Marcela Singh, Sonali Heinsbroek, Sigrid Haq, Imran Johnson, Simon Brown, Gordon D. Williams, David L. Taylor, Philip R. Martinez-Pomares, Luisa J Biol Chem Immunology The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through β-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate β-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and β-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection. American Society for Biochemistry and Molecular Biology 2011-03-11 2011-01-04 /pmc/articles/PMC3048669/ /pubmed/21205820 http://dx.doi.org/10.1074/jbc.M110.185025 Text en © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Immunology Gazi, Umut Rosas, Marcela Singh, Sonali Heinsbroek, Sigrid Haq, Imran Johnson, Simon Brown, Gordon D. Williams, David L. Taylor, Philip R. Martinez-Pomares, Luisa Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement |
title | Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement |
title_full | Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement |
title_fullStr | Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement |
title_full_unstemmed | Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement |
title_short | Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement |
title_sort | fungal recognition enhances mannose receptor shedding through dectin-1 engagement |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048669/ https://www.ncbi.nlm.nih.gov/pubmed/21205820 http://dx.doi.org/10.1074/jbc.M110.185025 |
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