title: 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.
abstract: 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.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Gorjestani
authors.forename: Bryant G
authors.initials: BG
authors.lastname: Darnay
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology / Q000502:physiology*; D002177:Candidiasis / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000276:immunology*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D037181:Lectins, C-Type; D020930:MAP Kinase Kinase Kinases; D048029:TNF Receptor-Associated Factor 6; D000099151:MAP Kinase Kinase Kinase 7