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Immunobiology. 2014 Jan;219(1):25-36. doi: 10.1016/j.imbio.2013.06.013. Epub 2013 Jul 4.

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

Author information

1
Department of Respiratory and Critical Care Medicine, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China.

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.

KEYWORDS:

Aspergillus fumigatus; B cell lymphoma 10; BCL10; C-type lectin receptors; CARD9; CLRs; Dectin-2; Fc receptor γ chain; FcRγ; GAPDH; IKK; IL-10; IL-12p70; IL-1β; IL-23p19; ITAM; IκBα; MALT1; MAPK; MOI; NADPH; NF-κB; PMA; ROS; Reactive oxygen species; SDS; SOD; Syk; Syk kinase; T helper cell type 1; T helper cell type 17; TLRs; TNF-α; Th1; Th17; Toll-like receptors; caspase recruitment domain 9; glyceraldehyde-3-phosphate dehydrogenase; immunoreceptor tyrosine-based activation-like motif; inhibitor of kappa B protein; interleukin-10; interleukin-12 subunit p70; interleukin-1β; interleukin-23 subunit p19; mitogen-activated protein kinase; mucosa-associated lymphoid tissue lymphoma-translocation gene 1; multiplicity of infection; nicotinamide-adenine dinucleotide phosphate; nuclear factor-kappa B; phorbol-12-myristate-13-acetate; reactive oxygen species; sodium dodecyl sulfate; spleen tyrosine kinase; superoxide dismutases; the IκBα kinase; tumor necrosis factor-α

PMID:
23886693
DOI:
10.1016/j.imbio.2013.06.013
[Indexed for MEDLINE]

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