Bacterial ligand of TLR2 signals Stat activation via induction of IRF1/2 and interferon-alpha production

Cell Signal. 2008 Oct;20(10):1873-81. doi: 10.1016/j.cellsig.2008.06.017. Epub 2008 Jul 2.

Abstract

Both type I interferons (IFNs) and interferon regulatory factors (IRFs) are well characterized in viral infections, whereas they are far less studied in bacterially activated toll-like receptor (TLR) pathways. Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses. In mouse macrophages, IRF2 was activated by lipoteichoic acid (LTA) of Staphylococcus aureus, resulting in up-regulation of IRF1 and rapid secretion of IFN-alpha. In addition, LTA-induced activation of Signal transducers and activators of transcription 1 (Stat1) and Stat3 via IRF2. The secretion of IFN-alpha was reduced in IRF2-silenced macrophages, resulting in a disappearance of tyrosine-phosphorylated Stat3 and a reduction of pro-inflammatory responses, despite induction of Mal adapter protein. These results provide a mechanistic insight into the pro-inflammatory responses against S. aureus LTA in mouse macrophages. IRFs can be intersecting factors of viral and bacterial responses in activated TLR signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Cell Line
  • Inflammation
  • Interferon Regulatory Factor-1 / metabolism*
  • Interferon Regulatory Factor-2 / metabolism*
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / metabolism
  • Interferon-beta / metabolism
  • Interferon-gamma / metabolism
  • Ligands
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Macrophages / metabolism
  • Mice
  • Myeloid Differentiation Factor 88 / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • STAT Transcription Factors / metabolism*
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction* / drug effects
  • Staphylococcus aureus / chemistry*
  • Teichoic Acids / pharmacology
  • Toll-Like Receptor 2 / metabolism*
  • Transcription Factors / metabolism

Substances

  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-2
  • Interferon-alpha
  • Irf1 protein, mouse
  • Irf2 protein, mouse
  • Ligands
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • STAT Transcription Factors
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Teichoic Acids
  • Toll-Like Receptor 2
  • Transcription Factors
  • lipoteichoic acid
  • Interferon-beta
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase