Role played by Toll-like receptors 2 and 4 in lipoteichoic acid-induced lung inflammation and coagulation

The cell wall of Streptococcus pneumoniae consists of lipoteichoic acid (LTA), which is released when pneumococci are killed by either the host immune system or antibiotic treatment. Release of excessive amounts of LTA has been implicated in the toxic sequelae of severe gram-positive infection by vi...

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Veröffentlicht in:The Journal of infectious diseases Jg. 197; H. 2; S. 245
Hauptverfasser: Dessing, Mark C, Schouten, Marcel, Draing, Christian, Levi, Marcel, von Aulock, Sonja, van der Poll, Tom
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 15.01.2008
Schlagworte:
Animals
Blood Coagulation - immunology
Blood Coagulation - physiology
Female
Inflammation - immunology
Inflammation - physiopathology
Lipopolysaccharide Receptors - metabolism
Lipopolysaccharides - immunology
Lipopolysaccharides - pharmacology
Lung - immunology
Lung - physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Specific Pathogen-Free Organisms
Streptococcus pneumoniae - immunology
Streptococcus pneumoniae - pathogenicity
Teichoic Acids - immunology
Teichoic Acids - pharmacology
Toll-Like Receptor 2 - metabolism
Toll-Like Receptor 4 - metabolism
ISSN:0022-1899
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Zusammenfassung:The cell wall of Streptococcus pneumoniae consists of lipoteichoic acid (LTA), which is released when pneumococci are killed by either the host immune system or antibiotic treatment. Release of excessive amounts of LTA has been implicated in the toxic sequelae of severe gram-positive infection by virtue of its proinflammatory properties. Several in vitro studies have shown that LTA is recognized by Toll-like receptor (TLR) 2 and CD14. Our objective here was to investigate the inflammatory properties of S. pneumoniae LTA in vivo and the role played by TLR2, TLR4, and CD14 therein. Wild-type (WT), TLR2 knockout (KO), TLR4 KO, TLR2x4 double-KO, and CD14 KO mice were intranasally inoculated with highly purified pneumococcal LTA. LTA induced a dose-dependent inflammatory response and activation of the coagulation and fibrinolytic pathways in a TLR2-dependent fashion. Surprisingly, TLR4 KO mice also displayed a somewhat diminished pulmonary inflammatory and coagulant response compared with WT mice, possibly as a result of absent TLR4 signaling through LTA-induced release of endogenous mediators. Pneumococcal LTA induces a profound inflammatory response and activation of the coagulation pathway in the lungs in vivo through a TLR2-dependent route, which likely is amplified by endogenous TLR4 ligands.
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ISSN:0022-1899
DOI:10.1086/524873