Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis 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 to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation. Journal of infectious diseases, 186(6), pp. 798-806. The University of Chicago Press 10.1086/342845

[img] Text
J Infect Dis.-2002-Echchannaoui-798-806.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (577kB) | Request a copy
[img]
Preview
Text
186-6-798.pdf - Other
Available under License Publisher holds Copyright.

Download (575kB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-1899

Publisher:

The University of Chicago Press

Language:

English

Submitter:

Stephen Leib

Date Deposited:

01 Sep 2014 10:03

Last Modified:

30 Oct 2019 07:37

Publisher DOI:

10.1086/342845

PubMed ID:

12198614

BORIS DOI:

10.7892/boris.52750

URI:

https://boris.unibe.ch/id/eprint/52750

Actions (login required)

Edit item Edit item
Provide Feedback