Document Type
Article
Publication Date
1-1-2015
Description
Over the last 40-yr, the majority of research on glucans has focused on β-(1→3)-glucans. Recent studies indicate that β-(1→6)-glucans may be even more potent immune modulators than β-(1→3)-glucans. Mechanisms by which β-(1→6)-glucans are recognized and modulate immunity are unknown. In this study, we examined the interaction of purified water-soluble β-(1→6)-glucans with macrophage cell lines and primary peritoneal macrophages and the cellular and molecular consequences of this interaction. Our results indicate the existence of a specific β-(1→6)-glucan receptor that internalizes the glucan ligand via a clathrin-dependent mechanism. We show that the known β-(1→3)-glucans receptors are not responsible for β-(1→6)-glucan recognition and interaction. The receptor-ligand uptake/interaction has an apparent dissociation constant (KD) of ∼4-μM, and was associated with phosphorylation of ERK and JNK but not Iκ-α or p38. Our results indicate that macrophage interaction with β-(1→6)-glucans may lead to modulation of genes associated with anti-fungal immunity and recruitment/activation of neutrophils. In summary, we show that macrophages specifically bind and internalize β-(1→6)-glucans followed by activation of intracellular signaling and modulation of anti-fungal immune response-related gene regulation. Thus, we conclude that the interaction between innate immunity and β-(1→6)-glucans may play an important role in shaping the anti-fungal immune response.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Noss, Ilka; Ozment, Tammy R.; Graves, Bridget M.; Kruppa, Michael D.; Rice, Peter J.; and Williams, David L.. 2015. Cellular and Molecular Mechanisms of Fungal β-(1→6)-Glucan in Macrophages. Innate Immunity. Vol.21(7). 759-769. https://doi.org/10.1177/1753425915595874 PMID: 26209532 ISSN: 1753-4259
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