期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 2, 页码 507-513出版社
WILEY
DOI: 10.1002/eji.200838687
关键词
DC; Dectin-1; Phagocytosis; Syk
类别
资金
- Cancer Research UK
- EMBO Longterm Fellowship
- HFSP Fellowship
Dectin-1 is a pattern-recognition receptor recognizing beta-(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 beta-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.
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