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

• DOI: 10.1084/jem.20020470
• Publication Date: 2002-09-30T17:03:17Z
• Authors: Gordon D. Brown; Philip R. Taylor; Delyth M. Reid; Janet A. Willment; David L. Williams; Luisa Martinez-Po...; Simon Y.C. Wong; Siamon Gordon
• Keywords: receptor; 610; Macrophage-1 Antigen; Nerve Tissue Proteins; macrophage; immunology; Mice; 03 medical and health sciences; Animals; Lectins, C-Type; Receptors, Immunologic; Glucans; 0303 health sciences; Macrophages; Brief Definitive Report; Zymosan; Membrane Proteins; R1; QR; 3. Good health; Mice, Inbred C57BL; glucans; lectin; Surgery; RB

Zymosan is a β-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 β-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 β-glucan receptor mediating this activity. To address the role of the recently described β-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 β-glucan–dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte β-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 β-glucans for therapeutic drug design.