This study investigates the role of Dectin-1 in the recognition of β-glucan by macrophages. Using specific carbohydrate inhibitors and a novel anti-Dectin-1 monoclonal antibody (mAb) 2A11, the researchers found that Dectin-1 is the predominant receptor involved in the nonopsonic recognition of zymosan, a β-glucan-rich particle. The study demonstrates that the macrophage mannose receptor (MR) and complement receptor 3 (CR3) do not play significant roles in this process. The results resolve the long-standing controversy regarding the identity of the β-glucan receptor and identify Dectin-1 as a key target for understanding the immunomodulatory properties of β-glucans in therapeutic drug design. The findings also highlight the importance of Dectin-1 in the innate immune response to β-glucans, which could have implications for the treatment of fungal infections.This study investigates the role of Dectin-1 in the recognition of β-glucan by macrophages. Using specific carbohydrate inhibitors and a novel anti-Dectin-1 monoclonal antibody (mAb) 2A11, the researchers found that Dectin-1 is the predominant receptor involved in the nonopsonic recognition of zymosan, a β-glucan-rich particle. The study demonstrates that the macrophage mannose receptor (MR) and complement receptor 3 (CR3) do not play significant roles in this process. The results resolve the long-standing controversy regarding the identity of the β-glucan receptor and identify Dectin-1 as a key target for understanding the immunomodulatory properties of β-glucans in therapeutic drug design. The findings also highlight the importance of Dectin-1 in the innate immune response to β-glucans, which could have implications for the treatment of fungal infections.