(1, 3)-β-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages

P Kankkunen, L Teirilä, J Rintahaka… - The Journal of …, 2010 - journals.aai.org
P Kankkunen, L Teirilä, J Rintahaka, H Alenius, H Wolff, S Matikainen
The Journal of Immunology, 2010journals.aai.org
Abstract β-glucans are naturally occurring polysaccharides that are the major cell wall
components of fungi. Recognition of β-glucans is mediated through a membrane-bound
pattern recognition receptor called dectin-1, and gene knock-out studies have shown that
dectin-1 plays an important role in antifungal immune response in vivo. In this report, we
have studied the effect of large particulate (1, 3)-β-glucans, including curdlan, glucan from
baker's yeast, paramylon, and zymosan, on inflammatory response in human macrophages …
Abstract
β-glucans are naturally occurring polysaccharides that are the major cell wall components of fungi. Recognition of β-glucans is mediated through a membrane-bound pattern recognition receptor called dectin-1, and gene knock-out studies have shown that dectin-1 plays an important role in antifungal immune response in vivo. In this report, we have studied the effect of large particulate (1, 3)-β-glucans, including curdlan, glucan from baker's yeast, paramylon, and zymosan, on inflammatory response in human macrophages. We show that β-glucans activate the transcription of the proinflammatory cytokine IL-1β through a dectin-1–dependent pathway in human macrophages. Moreover, dectin-1 receptor associated Syk tyrosine kinase was essential for β-glucan induced IL-1β mRNA expression. In contrast to LPS, β-glucans also strongly activated the secretion of IL-1β. This β-glucan triggered IL-1β release was abolished by cytochalasin D, an inhibitor of phagocytosis, demonstrating that cytosolic recognition of β-glucans is required for IL-1β response in human macrophages. RNA interference-mediated gene knockdown experiments demonstrated that cytoplasmic NLRP3 inflammasome is essential for β-glucan–induced IL-1β secretion. Moreover, our results suggest that β-glucan–induced NLRP3 inflammasome activation is dependent on the dectin-1/Syk signaling pathway. Furthermore, our results suggest that the lysosomal cathepsin B protease, the formation of reactive oxygen species, and the efflux of potassium are needed for β-glucan–induced NLRP3 inflammasome activation. In conclusion, our results show that β-glucans are recognized by membrane-associated dectin-1 and cytoplasmic NLRP3 inflammasome resulting in IL-1β gene transcription and IL-1β secretion in human macrophages, respectively.
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