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Publication : Internalization of Dectin-1 terminates induction of inflammatory responses.

First Author  Hernanz-Falcón P Year  2009
Journal  Eur J Immunol Volume  39
Issue  2 Pages  507-13
PubMed ID  19130473 Mgi Jnum  J:144508
Mgi Id  MGI:3831051 Doi  10.1002/eji.200838687
Citation  Hernanz-Falcon P, et al. (2009) Internalization of Dectin-1 terminates induction of inflammatory responses. Eur J Immunol 39(2):507-13
abstractText  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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