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Infection and Immunity, July 2001, p. 4561-4571, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4561-4571.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Endogenous Interleukin-10 Is Required for Prevention of a Hyperinflammatory Intracerebral Immune Response in Listeria monocytogenes Meningoencephalitis

Martina Deckert,1,dagger Sabine Soltek,2 Gernot Geginat,2 Sonja Lütjen,1,2 Manuel Montesinos-Rongen,1 Herbert Hof,2 and Dirk Schlüter2,*

Institut für Neuropathologie, Universitätsklinken Bonn, Bonn,1 and, Institut für Medizinische Mikrobiologie und Hygiene, Universität Heidelberg, Universitätsklinikum Mannheim, Mannheim,2 Germany

Received 9 January 2001/Returned for modification 22 February 2001/Accepted 3 April 2001

To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infections, we studied cerebral listeriosis in IL-10-deficient (IL-10-/-) and wild-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis. IL-10-/- mice succumbed to primary as well as secondary listeriosis, whereas WT mice were significantly protected from secondary listeriosis by prior intraperitoneal immunization with Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10-/- mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages. IL-10-/- mice recruited significantly increased numbers of leukocytes, in particular granulocytes, to the brain, and the intracerebral cytokine (tumor necrosis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synthase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory protein 1alpha [MIP-1alpha ], and MIP-1beta ) transcription was enhanced compared to that in WT mice. Despite this prominent hyperinflammation, the frequencies of intracerebral L. monocytogenes-specific CD8+ T cells were reduced and the intracerebral bacterial load was not reduced in IL-10-/- mice compared to WT mice. Following intraperitoneal infection, IL-10-/- mice exhibited hepatic hyperinflammation without better bacterial clearance; however, in contrast to the mice with cerebral listeriosis, they did not succumb, illustrating that intrinsic factors of the target organ have a strong impact on the course and outcome of the infection.

* Corresponding author: Mailing address: Institut für Medizinische Mikrobiologie und Hygiene, Universität Heidelberg, Universitätsklinikum Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. Phone: 49-621-383-2036. Fax: 49-621-383-3816. E-mail: dirk.schlueter{at}imh.ma.uni-heidelberg.de.

dagger Present address: Abteilung für Neuropathologie, Universität zu Köln, Cologne, Germany.

Infection and Immunity, July 2001, p. 4561-4571, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4561-4571.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.