Experimental autoimmune encephalomyelitis repressed by microglial paralysis

Frank L Heppner, Melanie Greter, Denis Marino, Jeppe Falsig, Gennadij Raivich, Nadine Hövelmeyer, Ari Waisman, Thomas Rülicke, Marco Prinz, Josef Priller, Burkhard Becher, Adriano Aguzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.

Original languageEnglish
Pages (from-to)146-52
Number of pages7
JournalNature Medicine
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Animals
  • Antiviral Agents
  • Bone Marrow Cells
  • Brain
  • CD11b Antigen
  • Chimera
  • Encephalomyelitis, Autoimmune, Experimental
  • Facial Nerve
  • Ganciclovir
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Microglia
  • Recombinant Fusion Proteins
  • Simplexvirus
  • Thymidine Kinase
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Experimental autoimmune encephalomyelitis repressed by microglial paralysis'. Together they form a unique fingerprint.

Cite this