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.
Echchannaoui
Hakim
H
Division of Infectious Diseases, Department of Research, University Hospital, Zürich, Switzerland. hakim.echchannaoui@unibas.ch
Frei
Karl
K
Schnell
Christian
C
Leib
Stephen L
SL
Zimmerli
Werner
W
Landmann
Regine
R
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