Dectin-1
A Major Receptor in Antifungal Immunity
Dectin-1 is a recently discovered pattern-recognition receptor that plays an important role in antifungal innate immunity. Dectin-1, which is expressed on phagocytes, is a specific receptor for β-glucans[1].
Zymosan
β-Glucans are glucose polymers found in the cell walls of fungi, such as zymosan (a cell wall preparation of Saccharomyces cerevisiae and Candida albicans). Dectin-1 binds and internalizes β-glucans and mediates the production of reactive oxygen species (ROS), activation of NF-κB and subsequent secretion of proinflammatory cytokines.
Zymosan, which is composed primarily of β-glucan, mannan, mannoprotein and chitin, induces immune responses that are both Dectin-1 and TLR2-dependent [2]. However, it is now clear that its β-glucan moiety triggers NF-κB activation only through Dectin-1 as treatment with hot alkali or organic solvents abrogates the TLR2-dependent response [2, 3].
Dectin-1 activation pathway
Dectin-1 is a type II transmembrane protein with a C-type lectin-like carbohydrate recognition domain (CRD) connected by a stalk to the transmembrane region, followed by a cytoplasmic tail containing an immunoreceptor tyrosinase-based activation motif (ITAM). Dectin-1 binds specifically to β-1,3 glucans and induces its own signaling pathway[4, 5]. After binding to its ligand, Dectin-1 is phosphorylated by a non-receptor tyrosinase kinase Src. Syk is then activated and induces the CARD9-Bcl10-Malt1 complex. This complex mediates the activation of NF-κB and the production of proinflammatory cytokines. Recent data suggest that Dectin-1 and TLR2/TLR6 signalings combine to enhance the responses triggered by each receptor [2, 5].
β-Glucans display various biological activities, including anti-tumor and anti-infective activities, that depend on their physicochemical properties. Further studies are needed to clarify the specificity of both Dectin-1 and β-glucans, thereby allowing to elucidate the immunomodulatory activities of β-Glucans.
References:
1. Brown GD. et al., 2003. Dectin-1 mediates the biological effects of betaglucans. J Exp Med. 197(9):1119-24.
2. Gantner BN. et al., 2003. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 197(9):1107-17.
3. Ikeda Y. et al., 2008. Dissociation of Toll-like receptor 2-mediated innate immune response to Zymosan by organic solvent-treatment without loss of Dectin-1 reactivity. Biol Pharm Bull. 31(1):13-8.
4. Gross O. et al., 2006. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature. 442(7103):651-6.
5. Dennehy KM & Brown GD., 2007. The role of the beta-glucan receptor Dectin-1 in control of fungal infection. J Leukoc Biol.;82(2):253-8.