Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation.
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.
Division of Infectious Diseases, Department of Research, University Hospital, Zürich, Switzerland. hakim.echchannaoui@unibas.ch
Hakim
H
Echchannaoui
Karl
K
Frei
Christian
C
Schnell
Stephen L
SL
Leib
Werner
W
Zimmerli
Regine
R
Landmann
D000818:Animals; D002443:Ceftriaxone / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D029721:Drosophila Proteins; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D016920:Meningitis, Bacterial / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D002511:Cephalosporins; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D002443:Ceftriaxone