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

Gordon D Brown, Philip R Taylor, Delyth M Reid, Janet A Willment, David L Williams, Luisa Martinez-Pomares, Simon Y C Wong, Siamon Gordon

Research output: Contribution to journalArticle

694 Citations (Scopus)

Abstract

Zymosan is a beta-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 beta-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 beta-glucan receptor mediating this activity. To address the role of the recently described beta-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 beta-glucan-dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte beta-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 beta-glucans for therapeutic drug design.
Original languageEnglish
Pages (from-to)407-12
Number of pages6
JournalJournal of Experimental Medicine
Volume196
Issue number3
Publication statusPublished - 2002

    Fingerprint

Keywords

  • Animals
  • Glucans
  • Macrophage-1 Antigen
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Zymosan

Cite this

Brown, G. D., Taylor, P. R., Reid, D. M., Willment, J. A., Williams, D. L., Martinez-Pomares, L., Wong, S. Y. C., & Gordon, S. (2002). Dectin-1 is a major beta-glucan receptor on macrophages. Journal of Experimental Medicine, 196(3), 407-12.