Experimental pneumococcal meningitis: impaired clearance of bacteria from the blood due to increased apoptosis in the spleen in Bcl-2-deficient mice.
Necrotic and apoptotic neuronal cell death can be found in pneumococcal meningitis. We investigated the role of Bcl-2 as an antiapoptotic gene product in pneumococcal meningitis using Bcl-2 knockout (Bcl-2(-/-)) mice. By using a model of pneumococcal meningitis induced by intracerebral infection, Bcl-2-deficient mice and control littermates were assessed by clinical score and a tight rope test at 0, 12, 24, 32, and 36 h after infection. Then mice were sacrificed, the bacterial titers in blood, spleen, and cerebellar homogenates were determined, and the brain and spleen were evaluated histologically. The Bcl-2-deficient mice developed more severe clinical illness, and there were significant differences in the clinical score at 24, 32, and 36 h and in the tight rope test at 12 and 32 h. The bacterial titers in the blood were greater in Bcl-2-deficient mice than in the controls (7.46 +/- 1.93 log CFU/ml versus 5.16 +/- 0.96 log CFU/ml [mean +/- standard deviation]; P < 0.01). Neuronal damage was most prominent in the hippocampal formation, but there were no significant differences between groups. In situ tailing revealed only a few apoptotic neurons in the brain. In the spleen, however, there were significantly more apoptotic leukocytes in Bcl-2-deficient mice than in controls (5,148 +/- 3,406 leukocytes/mm2 versus 1,070 +/- 395 leukocytes/mm2; P < 0.005). Bcl-2 appears to counteract sepsis-induced apoptosis of splenic lymphocytes, thereby enhancing clearance of bacteria from the blood.
Wellmer
Andreas
A
Department of Neurology, University of Göttingen, D-37075 Göttingen, Germany.
von Mering
Matthias
M
Spreer
Annette
A
Diem
Ricarda
R
Eiffert
Helmut
H
Noeske
Christiane
C
Bunkowski
Stefanie
S
Gold
Ralf
R
Nau
Roland
R
D000818:Animals; D017209:Apoptosis; D001769:Blood / Q000382:microbiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*
D019253:Proto-Oncogene Proteins c-bcl-2