Document Detail


Tumor necrosis factor receptor-associated factor 6 (TRAF6) and TGFβ-activated kinase 1 (TAK1) play essential roles in the C-type lectin receptor signaling in response to Candida albicans infection.
MedLine Citation:
PMID:  23148225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tumor necrosis factor receptor-associated factor 6 (TRAF6) and TGFβ-activated kinase 1 (TAK1) are considered as key intermediates in Toll-like receptor (TLR) signaling. However, the role of TRAF6 and TAK1 in C-type lectin receptors (CLRs) in response to fungal infection has not been studied. In this study, we have utilized macrophages derived from TRAF6 knock-out mice and myeloid-specific TAK1-deficient mice and determined the role of TRAF6 and TAK1 in CLR-induced signal transduction events. We demonstrate that TRAF6 and TAK1 are required for NF-κB and JNK activation, and expression of proinflammatory cytokines in response to Candida albicans infection. Our results highlight TRAF6 and TAK1 as key components in the signaling cascade downstream of C-type lectin receptors and as critical mediators of the anti-fungal immune response. Therefore, our studies provide a mechanistic understanding of the host immune response to C. albicans, which has a significant impact for the development of anti-fungal therapeutics and in understanding risk-factors and determining susceptibility to C. albicans infection.
Authors:
Sara Gorjestani; Bryant G Darnay; Xin Lin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  2013-03-25     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44143-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Candida albicans / immunology,  physiology*
Candidiasis / enzymology,  genetics,  immunology*
Cells, Cultured
Female
Humans
Lectins, C-Type / genetics,  immunology*
MAP Kinase Kinase Kinases / genetics,  immunology*
Macrophages / immunology,  microbiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction*
TNF Receptor-Associated Factor 6 / genetics,  immunology*
Grant Support
ID/Acronym/Agency:
R01AI050848/AI/NIAID NIH HHS; R01GM065899/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Lectins, C-Type; 0/TNF Receptor-Associated Factor 6; EC 2.7.11.25/MAP Kinase Kinase Kinases; EC 2.7.11.25/MAP kinase kinase kinase 7
Comments/Corrections

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