Toll-like receptor-2 deficiency is associated with enhanced brain TNF gene expression during pneumococcal meningitis

J Neuroimmunol. 2005 Nov;168(1-2):21-33. doi: 10.1016/j.jneuroim.2005.06.016.

Abstract

TNF is a marker of disease activity in bacterial meningitis. To investigate TNF modulation by Toll-like receptor-2 (TLR2), we studied temporal and anatomical expression patterns of TLR2 and TNF in a pneumococcal meningitis model in wild type (wt) and TLR2(-/-) mice. We show by in situ hybridization that transcripts of TLR2 and of the comolecules CD14, MD-2, TLR1/6 strongly increased and colocalized with TNF in CD45-positive infiltrating cells in the ventricles, corpus callosum and the meninges. TNF gene and protein expression was stronger in TLR2(-/-) than wt brains and associated with increased IkappaB expression suggesting that TLR2 is controlling inflammation via TNF regulation.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Northern / methods
  • Blotting, Western / methods
  • Brain / metabolism*
  • Brain / microbiology
  • Brain / pathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression Regulation / physiology*
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Leukocytes / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Listeria monocytogenes / pathogenicity
  • Lymphocyte Antigen 96 / metabolism
  • Meningitis, Pneumococcal / metabolism*
  • Meningitis, Pneumococcal / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Streptococcus pneumoniae / pathogenicity
  • Time Factors
  • Toll-Like Receptor 2 / deficiency*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • I kappa B beta protein
  • I-kappa B Proteins
  • Lipopolysaccharide Receptors
  • Lymphocyte Antigen 96
  • RNA, Messenger
  • Tlr11 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10