Internalization of Dectin-1 terminates induction of inflammatory responses.

Internalization of Dectin-1 terminates induction of inflammatory responses.
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DOI:
10.1002/eji.200838687
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发表时间:
2009-02
影响因子:
5.4
通讯作者:
Reis e Sousa, Caetano
Reis e Sousa, Caetano
中科院分区:
医学3区
文献类型:
--
作者:
Hernanz-Falcon, Patricia;Joffre, Olivier;Williams, David L.;Reis e Sousa, Caetano

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Dectin-1是一种识别真菌细胞壁上β-(1,3)-葡聚糖的模式识别受体。Dectin-1通过介导真菌颗粒的吞噬清除和诱导先天性应答基因的转录在真菌免疫中起重要作用。我们在这里表明,这两个过程是联系在一起的,Dectin-1的炎症信号被吞噬作用减弱。使用肌动蛋白聚合或发动蛋白抑制剂、大的不可吞噬的β-葡聚糖颗粒或吞噬能力差的细胞阻断Dectin-1配体依赖性内化,在所有情况下都导致下游信号传导途径的增强和持续激活,并最终产生高水平的促炎细胞因子。这些发现确立了吞噬作用不仅在病原体清除中,而且在模式识别受体信号传导的调节中的重要性,并强烈表明内化是减弱Dectin-1介导的促炎反应的第一步。
Dectin-1 is a pattern-recognition receptor recognizing β-(1,3)-glucans found on fungal cell walls. Dectin-1 plays an important role in immunity to fungi by mediating phagocytic clearance of fungal particles and inducing transcription of innate response genes. We show here that the two processes are linked and that Dectin-1 signalling for inflammation is attenuated by phagocytosis. Blocking Dectin-1 ligand-dependent internalization using either actin polymerization or dynamin inhibitors, large non-phagocytosable β-glucan particles or poorly phagocytic cells leads in all cases to enhanced and sustained activation of downstream signalling pathways and culminates in production of high levels of pro-inflammatory cytokines. These findings establish the importance of phagocytosis not only in the clearance of pathogens, but also in the modulation of pattern-recognition receptor signalling and strongly suggest that internalization is the first step to attenuation of Dectin-1-mediated pro-inflammatory responses.
Dectin-1介导β-葡聚糖的生物学作用。
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