Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis

Neurosci Lett. 2003 Mar 6;338(3):201-4. doi: 10.1016/s0304-3940(02)01406-4.

Abstract

Matrix metalloproteinase-9 (MMP-9) appears to contribute to blood-brain barrier damage and neuronal injury in bacterial meningitis. To further explore the function of MMP-9 in meningeal inflammation, we injected 10(4) colony forming units (CFU) of a Streptoccocus pneumoniae type 3 strain into the right forebrain of MMP-9 deficient mice (MMP-9(-/-), n=16) and wild-type controls (129 x B6, n=15). The clinical course of the disease, leukocyte recruitment into the subarachnoid space and bacterial titers in the brain did not differ. Yet, clearance of the bacteria from blood (log CFU/ml 4.7 [3.8/5.4] vs. 3.6 [3.0/4.0]; P=0.005) and spleen homogenates (log CFU/ml 5.3 [4.8/5.5] vs. 4.0 [2.8/4.7]; P=0.01) was reduced in MMP-9 deficient mice. A reduced systemic bacterial clearance of MMP-9(-/-) mice was confirmed in experimental S. pneumoniae peritonitis/sepsis. This implies a compromised systemic, but not intracerebral host response against S. pneumoniae in MMP-9 deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / microbiology
  • Brain / pathology
  • Matrix Metalloproteinase 9 / deficiency*
  • Matrix Metalloproteinase 9 / immunology*
  • Meningitis, Pneumococcal / immunology*
  • Meningitis, Pneumococcal / microbiology
  • Meningitis, Pneumococcal / pathology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Peritonitis / immunology
  • Peritonitis / microbiology
  • Pneumococcal Infections / blood
  • Pneumococcal Infections / immunology*
  • Sepsis / immunology
  • Sepsis / microbiology
  • Spleen / microbiology
  • Streptococcus pneumoniae / immunology
  • Streptococcus pneumoniae / isolation & purification

Substances

  • Matrix Metalloproteinase 9