Interferon-β production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans

Immunity. 2013 Jun 27;38(6):1176-86. doi: 10.1016/j.immuni.2013.05.010. Epub 2013 Jun 13.

Abstract

Type I interferon (IFN) is crucial during infection through its antiviral properties and by coordinating the immunocompetent cells involved in antiviral or antibacterial immunity. Type I IFN (IFN-α and IFN-β) is produced after virus or bacteria recognition by cytosolic receptors or membrane-bound TLR receptors following the activation of the transcription factors IRF3 or IRF7. IFN-β production after fungal infection was recently reported, although the underlying mechanism remains controversial. Here we describe that IFN-β production by dendritic cells (DCs) induced by Candida albicans is largely dependent on Dectin-1- and Dectin-2-mediated signaling. Dectin-1-induced IFN-β production required the tyrosine kinase Syk and the transcription factor IRF5. Type I IFN receptor-deficient mice had a lower survival after C. albicans infection, paralleled by defective renal neutrophil infiltration. IFN-β production by renal infiltrating leukocytes was severely reduced in C. albicans-infected mice with Syk-deficient DCs. These data indicate that Dectin-induced IFN-β production by renal DCs is crucial for defense against C. albicans infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / immunology*
  • Candidiasis / immunology*
  • Cell Movement / genetics
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Interferon Regulatory Factors / metabolism
  • Interferon-beta / genetics
  • Interferon-beta / metabolism*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney / immunology
  • Lectins, C-Type / metabolism*
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / genetics
  • Syk Kinase

Substances

  • Interferon Regulatory Factors
  • Intracellular Signaling Peptides and Proteins
  • Irf5 protein, mouse
  • Lectins, C-Type
  • dectin 1
  • Interferon-beta
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse