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Activation of the Innate Immune Receptor Dectin-1 upon Formation of a ‘Phagocytic Synapse’

Research Abstract

Helen S. Goodridge, Christopher N. Reyes, Courtney A. Becker, Tamiko R. Katsumoto, Jun Ma, Andrea J. Wolf, Nandita Bose, Anissa S. H. Chan, Andrew S. Magee, Michael E. Danielson, Arthur Weiss, John P. Vasilakos & David M. Underhill

Affiliations
IBD and Immunobiology Research Institute, 8700 Beverly Boulevard, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
Helen S. Goodridge, Christopher N. Reyes, Courtney A. Becker, Jun Ma, Andrea J. Wolf & David M. Underhill

Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, USA
Helen S. Goodridge

David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, University of California, Los Angeles, California 90095, USA
Helen S. Goodridge & David M. Underhill

Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, 513 Parnassus, University of California, San Francisco, California 94143, USA
Tamiko R. Katsumoto & Arthur Weiss

Biothera, 3388 Mike Collins Drive, Eagan, Minnesota 55121, USA
Nandita Bose, Anissa S. H. Chan, Andrew S. Magee, Michael E. Danielson & John P. Vasilakos

Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA
Arthur Weiss

Nature 472, 471–475 (28 April 2011) doi:10.1038/nature10071
Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects beta glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS)1, 2. In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate beta glucan polymers, Dectin-1 signalling is only activated by particulate beta glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded. The ‘phagocytic synapse’ now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required.

Source:

Published at wellmune.com on 28 April 2011

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