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J Immunol. 2010 Jun 1;184(11):6335-42. doi: 10.4049/jimmunol.0903019. Epub 2010 Apr 26.

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

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  • 1Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.

Abstract

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 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-1beta gene transcription and IL-1beta secretion in human macrophages, respectively.

PMID:
20421639
[PubMed - indexed for MEDLINE]
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