title: Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells.
abstract: Innate immune pattern recognition receptors play critical roles in pathogen detection and initiation of antimicrobial responses. We and others have previously demonstrated the importance of the beta-glucan receptor Dectin-1 in the recognition of pathogenic fungi by macrophages and dendritic cells and have elucidated some of the mechanisms by which Dectin-1 signals to coordinate the antifungal response. While Dectin-1 signals alone are sufficient to trigger phagocytosis and Src-Syk-mediated induction of antimicrobial reactive oxygen species, collaboration with TLR2 signaling enhances NF-kappaB activation and regulates cytokine production. In this study we demonstrate that Dectin-1 signaling can also directly modulate gene expression via activation of NFAT. Dectin-1 ligation by zymosan particles or live Candida albicans yeast triggers NFAT activation in macrophages and dendritic cells. Dectin-1-triggered NFAT activation plays a role in the induction of early growth response 2 and early growth response 3 transcription factors, and cyclooxygenase-2. Furthermore, we show that NFAT activation regulates IL-2, IL-10 and IL-12 p70 production by zymosan-stimulated dendritic cells. These data establish NFAT activation in myeloid cells as a novel mechanism of regulation of the innate antimicrobial response.
authors.affiliation: Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Goodridge
authors.forename: Randi M
authors.initials: RM
authors.lastname: Simmons
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D037181:Lectins, C-Type; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D015054:Zymosan / Q000276:immunology* / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D015054:Zymosan; D000099181:Dectin-1; C493486:Tlr2 protein, mouse