Dectin-1 Is A Major (cid:2) -Glucan Receptor On Macrophages

Zymosan is a (cid:2) -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 (cid:2) -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 (cid:2) -glucan receptor mediating this activity. To address the role of the recently described (cid:2) -glucan receptor, Dectin-1, we generated a novel anti–Dec-tin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively respon-sible for the (cid:2) -glucan–dependent, nonopsonic recognition of zymosan by primary macrophages. These findings define Dectin-1 as the leukocyte (cid:2) -glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this impor-tant molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of (cid:2) -glucans for therapeutic drug design.