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

By Gordon D. Brown, P. Taylor, Delyth M. Reid, J. Willment, David L. Williams, L. Martínez-Pomares, Simon Y. C. Wong, S. Gordon. Journal of Experimental Medicine, 2002

1,012 citations recorded by the source corpus.

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.

Subfields: Biotechnology, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/0ea7dd5c90857fee911a61c18c38cd143b18bb70

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Citations in the corpus

Toll-Like Receptor 2 Suppresses Immunity against Candida albicans through Induction of IL-10 and Regulatory T Cells (2004, background): “Surprisingly, the production of TNF and IL-1 was only marginally impaired in TLR2 / mice, suggesting that either other TLRs or receptors other than TLR such as mannose receptor (18), -glucan receptor (19), complement receptor 3 (20), or dendritic cell-specific intercellular adhesion molecule-grabbin”
Pathogen recognition and innate immunity. (2006, background): “Dectin-1 binds b-glucan and is the primary receptor on macrophages for phagocytosis of various fungi (Brown et al., 2002).”
Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. (2009, background): “Another pathogen recognition receptor is dectin-1, a bglucan-binding transmembrane protein that is highly expressed on macrophages (Brown et al., 2002).”
Characterization of β-Glucan Recognition Site on C-Type Lectin, Dectin 1 (2004, background): “albicans and zymosan from the cell wall of Saccharomyces cerevisiae (8, 9).”
Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. (2006, background): “Dectin-1 has been reported to be the major receptor for β-glucan (42), and recent studies have demonstrated that it forms a receptor complex with TLR2, amplifying its effects (24, 25).”
The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species (2020, background): “Mannans are considered pathogen associated molecular pattern (PAMP) ligands and many host receptors are known to participate in its recognition (Brown et al., 2002; Rubin-Bejerano et al., 2007).”