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

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  • Gordon D. Brown
    1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
  • Philip R. Taylor
    1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
  • Delyth M. Reid
    2The Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN, United Kingdom
  • Janet A. Willment
    1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
  • David L. Williams
    3Department of Surgery, James H. Quillen College of Medicine, Johnson City, TN 37614
  • Luisa Martinez-Pomares
    1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
  • Simon Y.C. Wong
    2The Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN, United Kingdom
  • Siamon Gordon
    1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom

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<jats:p>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.</jats:p>

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