Header

UZH-Logo

Maintenance Infos

Toll‐Like Receptor 2–Deficient Mice Are Highly Susceptible toStreptococcus pneumoniaeMeningitis because of Reduced Bacterial Clearing and Enhanced Inflammation


Echchannaoui, Hakim; Frei, Karl; Schnell, Christian; Leib, Stephen L; Zimmerli, Werner; Landmann, Regine (2002). Toll‐Like Receptor 2–Deficient Mice Are Highly Susceptible toStreptococcus pneumoniaeMeningitis because of Reduced Bacterial Clearing and Enhanced Inflammation. Journal of Infectious Diseases, 186(6):798-806.

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

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

Statistics

Citations

Dimensions.ai Metrics
226 citations in Web of Science®
239 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

10 downloads since deposited on 26 Sep 2018
3 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Health Sciences > Infectious Diseases
Language:English
Date:15 September 2002
Deposited On:26 Sep 2018 10:28
Last Modified:31 Jul 2020 02:28
Publisher:Oxford University Press
ISSN:0022-1899
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1086/342845
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101086342845 (Library Catalogue)

Download

Hybrid Open Access

Download PDF  'Toll‐Like Receptor 2–Deficient Mice Are Highly Susceptible toStreptococcus pneumoniaeMeningitis because of Reduced Bacterial Clearing and Enhanced Inflammation'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 575kB
View at publisher