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Infection and Immunity, June 2004, p. 3113-3119, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3113-3119.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

Andreas Wellmer,¹ Matthias von Mering,¹ Annette Spreer,¹ Ricarda Diem,¹ Helmut Eiffert,² Christiane Noeske,¹ Stefanie Bunkowski,¹ Ralf Gold,^3, and Roland Nau^1*

Department of Neurology,¹ Department of Bacteriology, University of Göttingen, D-37075 Göttingen,² Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany³

Received 8 August 2003/ Returned for modification 15 December 2003/ Accepted 1 March 2004

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.

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* Corresponding author. Mailing address: Department of Neurology, University Hospital, Robert-Koch-Str. 40, D-37075 Göttingen, Germany. Phone: 49-551-39 8455. Fax: 49-551-39 8405. E-mail: rnau{at}gwdg.de.

Editor: V. J. DiRita

Present address: Hertie Institute of MS Research, 37075 Göttingen, Germany.

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Infection and Immunity, June 2004, p. 3113-3119, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3113-3119.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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