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 IkappaB expression suggesting that TLR2 is controlling inflammation via TNF regulation.
Letiembre
Maryse
M
Division of Infectious Diseases, Department of Research, University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Echchannaoui
Hakim
H
Ferracin
Fabrizia
F
Rivest
Serge
S
Landmann
Regine
R
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008089:Listeria monocytogenes / Q000472:pathogenicity; D051218:Lymphocyte Antigen 96 / Q000378:metabolism; D008586:Meningitis, Pneumococcal / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000172:deficiency*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D012333:RNA, Messenger; C482903:Tlr11 protein, mouse; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10