Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells

J Immunol. 2007 Mar 1;178(5):3107-15. doi: 10.4049/jimmunol.178.5.3107.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Immunity, Innate / drug effects
  • Lectins, C-Type
  • Macrophages / immunology*
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • NFATC Transcription Factors / immunology*
  • Nerve Tissue Proteins / immunology*
  • Oligonucleotide Array Sequence Analysis
  • Phagocytosis / drug effects
  • Phagocytosis / immunology
  • Reactive Oxygen Species / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Toll-Like Receptor 2 / immunology
  • Zymosan / immunology*
  • Zymosan / pharmacology

Substances

  • Lectins, C-Type
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nerve Tissue Proteins
  • Reactive Oxygen Species
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • dectin 1
  • Zymosan