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Acta Neuropathologica

, Volume 111, Issue 6, pp 548–558 | Cite as

Regulation of microglial cell responses in murine Toxoplasma encephalitis by CD200/CD200 receptor interaction

  • Martina DeckertEmail author
  • Jonathon D. Sedgwick
  • Elena Fischer
  • Dirk Schlüter
Original Paper

Abstract

Under autoimmune inflammatory conditions within the brain, evidence suggests that neurons downregulate microglial activation through CD200/CD200R interaction, which reduces disease severity. To gain insight into the regulation of intracerebral immune reactions by resident brain cells in chronic cerebral infections, the expression of the CD200 antigen and the CD200R as well as the functional role of CD200/CD200R interactions were characterized in murine Toxoplasma encephalitis. In the normal brain of C57BL/6 wild type mice, CD200 was ubiquitously expressed on neurons, their axons, cerebral endothelial cells, and plexus macrophages. CD200R was expressed at very low levels on cerebral macrophages and microglia without differences between CD200−/− and wild type mice. Infection of C57BL/6 mice with Toxoplasma gondii induced an upregulation of CD200R on microglia and of CD200 on blood vessel endothelial cells. In Toxoplasma encephalitis of CD200−/− mice, microglial cell numbers strongly increased due to an enhanced proliferation indicated by increased Ki-67 immunoreactivity. In addition, microglial activation was increased in CD200−/− mice as evidenced by a further upregulation of already high MHC class II levels as well as an increased expression of the anti-parasitic effector molecules, TNF and iNOS. The increased microglial cell activation resulted in a reduced intracerebral parasite burden and an increased survival rate. Thus, in Toxoplasma encephalitis, microglial activity was regulated via CD200/CD200R-mediated interaction further pointing to an intrinsic regulation of brain resident cells under inflammatory CNS conditions.

Keywords

Toxoplasma Encephalitis Microglia Neuron CD200 

Notes

Acknowledgement

This study was supported by a grant from the Deutsche Forschungsgemeinschaft (grant no.: De 485/6-3).

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Martina Deckert
    • 1
    Email author
  • Jonathon D. Sedgwick
    • 2
  • Elena Fischer
    • 1
  • Dirk Schlüter
    • 3
    • 4
  1. 1.Department of NeuropathologyUniversity of CologneCologneGermany
  2. 2.Eli Lilly and CompanyIndianapolisUSA
  3. 3.Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum MannheimUniversität HeidelbergMannheimGermany
  4. 4.Institut für Medizinische MikrobiologieOtto-von-Guericke Universität MagdeburgMagdeburgGermany

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