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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Fungal recognition enhances mannose receptor shedding through dectin-1 engagement
Journal of Biological Chemistry, Volume 286, No. 10, Year 2011
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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 MRis 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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors & Co-Authors
Rosas, Marcela
United Kingdom, Cardiff
Cardiff University School of Medicine
Singh, Sonali
United Kingdom, Nottingham
Queen's Medical Centre
Heinsbroek, Sigrid E.M.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Johnson, Simon R.
United Kingdom, Nottingham
Queen's Medical Centre
Brown, Gordon D.A.
United Kingdom, Aberdeen
University of Aberdeen
Williams, David L.
United Kingdom, Nottingham
Queen's Medical Centre
Taylor, Philip Russel
United States, Johnson
East Tennessee State University
Martinez-Pomares Luisa, Luisa
United Kingdom, Nottingham
Queen's Medical Centre
Statistics
Citations: 60
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1074/jbc.M110.185025
ISSN:
1083351X