Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement

Gazi, U., Rosas, Marcela ORCID: https://orcid.org/0000-0002-9442-9638, Singh, S., Heinsbroek, S., Haq, I., Johnson, S., Brown, G. D., Williams, D. L., Taylor, Philip Russel ORCID: https://orcid.org/0000-0003-0163-1421 and Martinez-Pomares, L. 2011. Fungal Recognition Enhances Mannose Receptor Shedding through Dectin-1 Engagement. Journal of Biological Chemistry 286 (10) , pp. 7822-7829. 10.1074/jbc.M110.185025

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	ADAM; ADAMTS; Fungi; Inflammation; Lectin; Macrophage; Metalloprotease; Mouse; Shedding
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	19 Oct 2022 10:44
URI:	https://orca.cardiff.ac.uk/id/eprint/25395

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