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

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 IκB expression suggesting that TLR2 is controlling inflammation via TNF regulation.