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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....

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Autores principales: Gazi, Umut, Rosas, Marcela, Singh, Sonali, Heinsbroek, Sigrid, Haq, Imran, Johnson, Simon, Brown, Gordon D., Williams, David L., Taylor, Philip R., Martinez-Pomares, Luisa
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2011
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.
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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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