The Journal of Experimental Medicine
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Published online 29 July 2002 doi:10.1084/jem.20020470
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© Rockefeller University Press, 0022-1007/2002/8/407/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002 407-412

Brief Definitive Report

Dectin-1 Is A Major ß-Glucan Receptor On Macrophages

Gordon D. Brown1, Philip R. Taylor1, Delyth M. Reid2, Janet A. Willment1, David L. Williams3, Luisa Martinez-Pomares1, Simon Y.C. Wong2 and Siamon Gordon1

1 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
2 The Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN, United Kingdom
3 Department of Surgery, James H. Quillen College of Medicine, Johnson City, TN 37614

Address correspondence to Dr. Gordon D. Brown, Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford OX1 3RE, UK. Phone: 44-1865-27-5522; Fax: 44-1865-27-5515; E-mail: gbrown{at}molbiol.ox.ac.uk

Zymosan is a ß-glucan– and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a ß-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the ß-glucan receptor mediating this activity. To address the role of the recently described ß-glucan receptor, Dectin-1, we generated a novel anti–Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the ß-glucan–dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte ß-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of ß-glucans for therapeutic drug design.

Key Words: lectin • macrophage • receptor • immunology • glucans


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