期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 213, 期 6, 页码 1047-1059出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20151000
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资金
- European Research Council (ERC) [250356]
- European Union (NEU RIN OX)
- Swiss National Foundation
- Swiss Initiative in Systems Biology, SystemsX.ch (PrionX, SynucleiX)
- Novartis Research Foundation
- Gelu Foundation
- Klinische Forschungsschwerpunkte (small RNAs and Human Hemato-Lymphatic Diseases)
- Young Scientist Stipend of the Ernst-Jung Foundation
- Career Development Award of the Stavros Niarchos Foundation
- European Research Council (ERC) [250356] Funding Source: European Research Council (ERC)
Microglial activation is a hallmark of most neurodegenerative disorders, and is particularly conspicuous in prion diseases. However, the role of microglia, which function as both primary immune effector cells and professional phagocytes in the central nervous system, remains contentious in the context of neurodegeneration. Here, we evaluated the effect of microglial depletion/deficiency on prion pathogenesis. We found that ganciclovir-mediated microglial ablation on tga20/CD11b-thymidine kinase of Herpes simplex virus (HSVTK) cerebellar organotypic cultured slices markedly aggravated prion-induced neurotoxicity. A similar deterioration of disease was recapitulated in in vivo microglial depletion in prion-infected tga20/ CD11b-HSVTK mice. Additionally, deficiency of microglia in interleukin 34 knockout (IL34(-/-)) mice again resulted in significantly augmented proteinase K-resistant prion protein deposition and accelerated prion disease progression. These results provide unambiguous evidence for a general protective role of microglia in prion pathogenesis.
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