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Type I interferon protects neurons from prions in in vivo models


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Title: Type I interferon protects neurons from prions in in vivo models
Authors: Ishibashi, Daisuke / Homma, Takujiro / Nakagaki, Takehiro / Fuse, Takayuki / Sano, Kazunori / Satoh, Katsuya / Mori, Tsuyoshi / Atarashi, Ryuichiro / Nishida, Noriyuki
Issue Date: 7-Feb-2019
Publisher: Oxford University Press
Citation: Brain : a journal of neurology, 142(4), pp.1035-1050; 2019
Abstract: Infectious prions comprising abnormal prion protein, which is produced by structural conversion of normal prion protein, are responsible for transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease in humans. Prions are infectious agents that do not possess a genome and the pathogenic protein was not thought to evoke any immune response. Although we previously reported that interferon regulatory factor 3 (IRF3) was likely to be involved in the pathogenesis of prion diseases, suggesting the protective role of host innate immune responses mediated by IRF3 signalling, this remained to be clarified. Here, we investigated the reciprocal interactions of type I interferon evoked by IRF3 activation and prion infection and found that infecting prions cause the suppression of endogenous interferon expression. Conversely, treatment with recombinant interferons in an ex vivo model was able to inhibit prion infection. In addition, cells and mice deficient in type I interferon receptor (subunit interferon alpha/beta receptor 1), exhibited higher susceptibility to 22L-prion infection. Moreover, in in vivo and ex vivo prion-infected models, treatment with RO8191, a selective type I interferon receptor agonist, inhibited prion invasion and prolonged the survival period of infected mice. Taken together, these data indicated that the interferon signalling interferes with prion propagation and some interferon-stimulated genes might play protective roles in the brain. These findings may allow for the development of new strategies to combat fatal diseases.
Keywords: prion infection / type I interferon (I-IFN) / innate immune system
URI: http://hdl.handle.net/10069/39175
ISSN: 00068950
DOI: 10.1093/brain/awz016
Rights: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.For commercial re-use, please contact journals.permissions@oup.com
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39175

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