(1,3)-β-Glucans Activate Both Dectin-1 and NLRP3 Inflammasome in Human Macrophages
(1,3)-β-Glucans Activate Both Dectin-1 and NLRP3 Inflammasome in Human Macrophages
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DOI：
10.4049/jimmunol.0903019
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Matikainen, Sampsa
中科院分区：
文献类型：
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作者：
Kankkunen, Paivi;Teirila, Laura;Matikainen, Sampsa
β-葡聚糖是天然存在的多糖，是真菌的主要细胞壁成分。 β-葡聚糖的识别是通过一种称为 dectin-1 的膜结合模式识别受体介导的，基因敲除研究表明 dectin-1 在体内抗真菌免疫反应中发挥着重要作用。在本报告中，我们研究了大颗粒 (1,3)-β-葡聚糖（包括凝乳胶、面包酵母葡聚糖、裸藻淀粉和酵母聚糖）对人类巨噬细胞炎症反应的影响。我们发现，β-葡聚糖通过人巨噬细胞中的 dectin-1 依赖性途径激活促炎细胞因子 IL-1 β 的转录。此外，dectin-1 受体相关的 Syk 酪氨酸激酶对于 β-葡聚糖诱导的 IL-1 β mRNA 表达至关重要。与LPS相反，β-葡聚糖也强烈激活IL-1β的分泌。这种 β-葡聚糖触发的 IL-1 β 释放被细胞松弛素 D（一种吞噬作用抑制剂）消除，这表明细胞溶质识别 β-葡聚糖是人巨噬细胞中 IL-1 β 反应所必需的。 RNA 干扰介导的基因敲低实验表明，细胞质 NLRP3 炎性体对于 β-葡聚糖诱导的 IL-1 β 分泌至关重要。此外，我们的结果表明，β-葡聚糖诱导的 NLRP3 炎性体激活依赖于 dectin-1/Syk 信号通路。此外，我们的结果表明，β-葡聚糖诱导的 NLRP3 炎性体激活需要溶酶体组织蛋白酶 B 蛋白酶、活性氧的形成和钾的流出。总之，我们的结果表明，β-葡聚糖被膜相关的 dectin-1 和细胞质 NLRP3 炎性体识别，分别导致人巨噬细胞中的 IL-1 β 基因转录和 IL-1 β 分泌。免疫学杂志，2010，184：6335-6342。
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-1 beta through a dectin-1-dependent pathway in human macrophages. Moreover, dectin-1 receptor associated Syk tyrosine kinase was essential for beta-glucan induced IL-1 beta mRNA expression. In contrast to LPS, beta-glucans also strongly activated the secretion of IL-1 beta. This beta-glucan triggered IL-1 beta release was abolished by cytochalasin D, an inhibitor of phagocytosis, demonstrating that cytosolic recognition of beta-glucans is required for IL-1 beta response in human macrophages. RNA interference-mediated gene knockdown experiments demonstrated that cytoplasmic NLRP3 inflammasome is essential for beta-glucan-induced IL-1 beta 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 reactive oxygen species, and the efflux of potassium are needed for beta-glucan-induced NLRP3 inflammasome activation. In conclusion, our results show that beta-glucans are recognized by membrane-associated dectin-1 and cytoplasmic NLRP3 inflammasome resulting in IL-1 beta gene transcription and IL-1 beta secretion in human macrophages, respectively. The Journal of Immunology, 2010, 184: 6335-6342.