Dectin-1 is a major β-glucan receptor on macrophages

GD Brown, PR Taylor, DM Reid, JA Willment… - The Journal of …, 2002 - rupress.org
GD Brown, PR Taylor, DM Reid, JA Willment, DL Williams, L Martinez-Pomares, SYC Wong…
The Journal of experimental medicine, 2002rupress.org
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 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.
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