Activation of NF-κB and respiratory burst following Aspergillus fumigatus stimulation of macrophages.

Abstract

Dectin-2, a C-type lectin receptor (CLR), plays an essential role in mediating nuclear factor-kappa B (NF-κB) 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-κB 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 IκBα (inhibitor of kappa B protein) phosphorylation and NF-κB activation following A. fumigatus stimulation in a time dependent manner. Silencing of Dectin-2 and Syk as well as Syk inhibition blocks NF-κB 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 IκBα kinase phosphorylation, NF-κB activation, and ROS production mediated by Dectin-2 activation in response to A. fumigatus infection.

• Authors: He Sun, Xiao-yong Xu, Xiao-li Tian, Hong-tao Shao, Xiao-dong Wu, Quan Wang, Xin Su, Yi Shi
• Journal: Immunobiology (Immunobiology) Vol. 219 Issue 1 Pg. 25-36 (Jan 2014) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 23886693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier GmbH. All rights reserved.

Chemical References

• Cytokines
• Intracellular Signaling Peptides and Proteins
• Lectins, C-Type
• NF-kappa B
• Reactive Oxygen Species
• Protein-Tyrosine Kinases
• SYK protein, human
• Syk Kinase
• I-kappa B Kinase

Topics

• Aspergillus fumigatus (immunology, physiology)
• Blotting, Western
• Cell Line, Tumor
• Cytokines (genetics, immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression (immunology)
• Host-Pathogen Interactions (immunology)
• Humans
• Hyphae (immunology, physiology)
• I-kappa B Kinase (genetics, immunology, metabolism)
• Intracellular Signaling Peptides and Proteins (genetics, immunology, metabolism)
• Lectins, C-Type (genetics, immunology, metabolism)
• Macrophages (immunology, metabolism, microbiology)
• NF-kappa B (genetics, immunology, metabolism)
• Phosphorylation (immunology)
• Protein-Tyrosine Kinases (genetics, immunology, metabolism)
• RNA Interference
• Reactive Oxygen Species (immunology, metabolism)
• Respiratory Burst (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Spores, Fungal (immunology, physiology)
• Syk Kinase
• Time Factors