Volume 2 Supplement 1

Infectious diseases of the nervous system: pathogenesis and worldwide impact

Open Access

Astrocyte gp130-expression is critical for the control of Toxoplasma encephalitis

  • Katrin Drögemüller1,
  • Ulrike Helmuth1,
  • Anna Brunn2,
  • Monika Sakowicz-Burkiewicz1, 2,
  • Dirk Reinhold3,
  • David H Gutmann4,
  • Werner Mueller5, 6,
  • Martina Deckert2 and
  • Dirk Schlüter1Email author
BMC Proceedings20082(Suppl 1):S10

DOI: 10.1186/1753-6561-2-s1-s10

Published: 23 September 2008

Toxoplasma (T.) gondii infects astrocytes, neurons and microglia cells in the CNS and, after acute encephalitis, persists within neurons. Robust astrocyte activation is a hallmark of Toxoplasma encephalitis (TE); however, the in vivo function of astrocytes is largely unknown. To study their role in TE, we generated C57BL/6 GFAP-Cre gp130fl/fl mice, which lack gp130, the signal transducing receptor for IL-6 family cytokines, in their astrocytes. In TE of wildtype mice, the gp130 ligands IL-6, IL-11, IL-27, LIF, oncostatin M, ciliary neurotrophic factor, B cell stimulating factor, and cardiotrophin-1 were upregulated. In addition, GFAP+ astrocytes of gp130fl/fl control mice were activated, increased in number, and efficiently restricted inflammatory lesions and parasites, thereby, contributing to survival from TE. In contrast, T. gondii-infected GFAP-Cre gp130fl/fl mice lost GFAP+ astrocytes in inflammatory lesions resulting in an inefficient containment of inflammatory lesions, impaired parasite control and, ultimately, a lethal necrotizing TE. Production of IFN-gamma and IGTP, which mediate parasite control in astrocytes, were even increased in GFAP-Cre gp130fl/fl mice indicating that instead of the direct anti-parasitic effect the immunoregulatory function of GFAP-Cre gp130fl/fl astrocytes was disturbed. Correspondingly, in vitro infected GFAP-Cre gp130fl/fl astrocytes inhibited growth of T. gondii efficiently after stimulation with IFN-gamma, whereas neighbouring non-infected and TNF-stimulated GFAP-Cre gp130fl/fl astrocytes became apoptotic. Collectively, these are the first experiments demonstrating a crucial function of astrocytes in CNS infection.

Authors’ Affiliations

Institut für Medizinische Mikrobiologie, OvG Universität Magdeburg
Abteilung für Neuropathologie, Universität zu Köln
Institut für Immunologie, OvG Universität Magdeburg
Department of Neurology, Washington University School of Medicine
Helmholtz-Zentrum für Infektionsforschung
University of Manchester


© Drögemüller et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.