Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis.
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.
Böttcher
Tobias
T
Department of Neurology, Georg-August-University, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.
Spreer
Annette
A
Azeh
Ivo
I
Nau
Roland
R
Gerber
Joachim
J
D000818:Animals; D001921:Brain / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000276:immunology*; D008586:Meningitis, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification
D020780:Matrix Metalloproteinase 9