Dectin-1 is a major beta-glucan receptor on macrophages.
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.
Brown
Gordon D
GD
Sir William Dunn School of Pathology, University of Oxford, United Kingdom. gbrown@molbiol.ox.ac.uk
Taylor
Philip R
PR
Reid
Delyth M
DM
Willment
Janet A
JA
Williams
David L
DL
Martinez-Pomares
Luisa
L
Wong
Simon Y C
SY
Gordon
Siamon
S
D000818:Animals; D005936:Glucans / Q000494:pharmacology; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen / Q000502:physiology; D008264:Macrophages / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis*; D015054:Zymosan / Q000378:metabolism; D000099181:Dectin-1
D005936:Glucans; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D015054:Zymosan; D000099181:Dectin-1; C045268:beta-glucan receptor