Protective role of MyD88-independent innate immune responses against prion infection.
Protective role of MyD88-independent innate immune responses against prion infection.
复制标题
对prion感染的独立于MyD88的先天免疫反应的保护作用。
作者：
Ishibashi D;Atarashi R;Nishida N
尽管最近在对普恩病毒疾病的理解上取得了进展，但对普恩病毒的宿主防御机制知之甚少。虽然长期以来认为I型干扰素(IFN-I)对病毒感染没有保护作用，但天然免疫中的某些关键分子，如Toll样受体(TLR4)似乎参与了宿主的免疫反应。为此，我们决定将重点放在TLRs上，并研究转录因子干扰素调节因子3(IRF3)的作用，因为TLRs的主要适配子信号分子MyD88的缺失对感染Prion的小鼠的生存没有任何影响。有趣的是，接种了IRF3基因敲除的Pron的小鼠的存活期明显比野生型小鼠短。此外，IRF3的刺激抑制了PrPSc在持续感染Prion的细胞中的复制，从头开始的Prion感染实验表明，IRF3的过表达可以使宿主细胞对Prion感染产生抵抗力。我们的工作表明，IRF3可能在抵抗Pron病原体入侵的先天免疫反应中发挥关键作用。激活的IRF3可以上调包括干扰素-I在内的多种抗病原体因子的表达，并诱导序贯反应。虽然IRF3介导的抗病毒机制尚不清楚，但某些干扰素应答基因可能参与了病毒的抗病毒宿主防御机制。
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 wild-type 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.
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影响因子：
5.8
作者：
Takeuchi, O;Akira, S
通讯作者：
Akira, S
影响因子：
4.2
作者：
Tal, Y;Souan, L;Mor, F
通讯作者：
Mor, F
DOI：
10.1073/pnas.0602460103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Delhaye, Sophie;Paul, Sophie;Michiels, Thomas
通讯作者：
Michiels, Thomas
影响因子：
56.9
作者：
Nishida, N;Katamine, S;Manuelidis, L
通讯作者：
Manuelidis, L
影响因子：
5.4
作者：
Riemer, C;Queck, I;Baier, M
通讯作者：
Baier, M