Protective role of MyD88-independent innate immune responses against prion infection
Abstract
Despite recent progress in the understanding of prion diseases, little is known about the host-defense mechanisms against prion. Although it has long been thought that type I interferon (IFN-I) has no protective effect on prion infection, certain key molecules in innate immunity such as toll-like receptor (TLR) 4 seemed to be involved in the host response. For this reason we decided to focus on TLRs and investigate the role of a transcription factor, interferon regulatory factor 3 (IRF3), because the absence of MyD88, a major adaptor signaling molecule of TLRs, has no effect on the survival of prion infected mice. Intriguingly, survival periods of prion inoculated IRF3-knockout mice became significantly shorter than those of wildtype mice. In addition, IRF3 stimulation inhibited PrPSc replication in prion persistently- infected cells, and a de novo prion infection assay revealed that IRF3-overexpression could make host cells resistant to prion infection. Our work suggests that IRF3 may play a key role in innate immune responses against invasion of prion pathogens. Activated IRF3 could upregulate several anti-pathogen factors, including IFN-I, and induce sequential responses. Although the mechanism for the anti-prion effects mediated by IRF3 has yet to be clarified, certain interferon responsive genes might be involved in the anti-prion host-defense mechanism.
Prion, 6(5), pp.443-446; 2012
Journal
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- Prion
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Prion 6 (5), 443-446, 2012-11
Landes Bioscience
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Keywords
Details 詳細情報について
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- CRID
- 1050005822286730240
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- NII Article ID
- 120006985798
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- ISSN
- 19336896
- 1933690X
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- HANDLE
- 10069/31113
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN