Abstract
Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ceftriaxone / therapeutic use
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Cephalosporins / therapeutic use
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Disease Models, Animal
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Disease Susceptibility*
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Drosophila Proteins*
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Inflammation / genetics
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Inflammation / immunology
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Inflammation / microbiology
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Inflammation / pathology
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Listeria monocytogenes / genetics
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Listeria monocytogenes / immunology
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Listeriosis / genetics
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Listeriosis / immunology
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Membrane Glycoproteins / deficiency*
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Membrane Glycoproteins / genetics
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Meningitis, Bacterial / genetics*
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Meningitis, Bacterial / immunology*
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Meningitis, Bacterial / microbiology
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Meningitis, Bacterial / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Pneumococcal Infections / genetics
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Pneumococcal Infections / immunology
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Pneumococcal Infections / microbiology
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Pneumococcal Infections / pathology
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Receptors, Cell Surface / deficiency*
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Receptors, Cell Surface / genetics
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Streptococcus pneumoniae / immunology*
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Time Factors
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Toll-Like Receptor 2
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Toll-Like Receptors
Substances
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Cephalosporins
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Drosophila Proteins
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Membrane Glycoproteins
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Receptors, Cell Surface
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Toll-Like Receptor 2
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Toll-Like Receptors
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Ceftriaxone