(1,3)-β-Glucans Activate Both Dectin-1 and NLRP3 Inflammasome in Human Macrophages

作者：Päivi Kankkunen, Laura Teirilä, Johanna Rintahaka, Harri Tapio Alenius, Henrik J. Wolff, Sampsa Matikainen · 发表于：The Journal of Immunology · 年份：2010 · DOI：10.4049/jimmunol.0903019 · 被引用次数：276 · 研究领域：Polysaccharides and Plant Cell Walls、Inflammasome and immune disorders、Galectins and Cancer Biology

beta-Glucans are naturally occurring polysaccharides that are the major cell wall components of fungi. Recognition of beta-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)-beta-glucans, including curdlan, glucan from baker's yeast, paramylon, and zymosan, on inflammatory response in human macrophages. We show that beta-glucans activate the transcription of the proinflammatory cytokine IL-1beta through a dectin-1-dependent pathway in human macrophages. Moreover, dectin-1 receptor associated Syk tyrosine kinase was essential for beta-glucan induced IL-1beta mRNA expression. In contrast to LPS, beta-glucans also strongly activated the secretion of IL-1beta. This beta-glucan triggered IL-1beta release was abolished by cytochalasin D, an inhibitor of phagocytosis, demonstrating that cytosolic recognition of beta-glucans is required for IL-1beta response in human macrophages. RNA interference-mediated gene knockdown experiments demonstrated that cytoplasmic NLRP3 inflammasome is essential for beta-glucan-induced IL-1beta secretion. Moreover, our results suggest that beta-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 rea...