Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation

J Infect Dis. 2002 Sep 15;186(6):798-806. doi: 10.1086/342845. Epub 2002 Aug 16.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceftriaxone / therapeutic use
  • Cephalosporins / therapeutic use
  • Disease Models, Animal
  • Disease Susceptibility*
  • Drosophila Proteins*
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / microbiology
  • Inflammation / pathology
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology
  • Listeriosis / genetics
  • Listeriosis / immunology
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Meningitis, Bacterial / genetics*
  • Meningitis, Bacterial / immunology*
  • Meningitis, Bacterial / microbiology
  • Meningitis, Bacterial / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumococcal Infections / genetics
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / microbiology
  • Pneumococcal Infections / pathology
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / genetics
  • Streptococcus pneumoniae / immunology*
  • Time Factors
  • Toll-Like Receptor 2
  • Toll-Like Receptors

Substances

  • Cephalosporins
  • Drosophila Proteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Ceftriaxone