期刊
IMMUNOBIOLOGY
卷 219, 期 1, 页码 25-36出版社
ELSEVIER GMBH
DOI: 10.1016/j.imbio.2013.06.013
关键词
Aspergillus fumigatus; Dectin-2; NF-kappa B; Reactive oxygen species; Syk kinase
类别
资金
- National Natural Science Foundation of China [81000003, 81270064, 81200063]
Dectin-2, a C-type lectin receptor (CLR), plays an essential role in mediating nuclear factor-kappa B (NF-kappa B) activation and anti-fungal immunity in response to Candida albicans infection. However, the molecular mechanisms and function of Dectin-2 signaling in response to infection by the pathogenic fungus Aspergillus fumigatus have not been characterized. In order to characterize Dectin-2 signaling in response to A. fumigatus infection, activation of Dectin-2 was analyzed at both transcriptional and translational levels. Spleen tyrosine kinase (Syk) phosphorylation, NF-kappa B activation and cytokine production downstream of Dectin-2 activation were also investigated. In addition, Dectin-2-Syk function and its ability to mediate reactive oxygen species (ROS) production and elimination of A. fumigatus conidia was examined. We demonstrate that Syk is involved in Dectin-2-induced I kappa B alpha (inhibitor of kappa B protein) phosphorylation and NF-kappa B activation following A. fumigatus stimulation in a time dependent manner. Silencing of Dectin-2 and Syk as well as Syk inhibition blocks NF-kappa B activation and cytokine secretion. Furthermore, the killing of A.fumigatus conidia and ROS production are significantly affected by Dectin-2 or Syk silencing as well as Syk inhibition. Swelling and germination of the fungus followed by hyphae formation and not the resting and heat-inactivated form of A.fumigatus mediate the activation of Dectin-2 signaling. In conclusion, Syk plays an essential role in I kappa B alpha kinase phosphorylation, NF-kappa B activation, and ROS production mediated by Dectin-2 activation in response to A. fumigatus infection. (C) 2013 Elsevier GmbH. All rights reserved.
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