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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

TLR3 signaling is either protective or pathogenic for the development of Theiler's virus-induced demyelinating disease depending on the time of viral infection

http://hdl.handle.net/10091/17620
http://hdl.handle.net/10091/17620
75f45076-39c9-4a79-bb54-3da0359ac499
名前 / ファイル ライセンス アクション
TLR3_signaling_either_protective_pathogenic.pdf.orefma1.pdf TLR3_signaling_either_protective_pathogenic.pdf.orefma1.pdf (8.1 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2014-06-20
タイトル
タイトル TLR3 signaling is either protective or pathogenic for the development of Theiler's virus-induced demyelinating disease depending on the time of viral infection
言語
言語 eng
DOI
関連識別子 https://doi.org/10.1186/1742-2094-8-178
関連名称 10.1186/1742-2094-8-178
キーワード
主題 TLR3, TMEV, demyelination, CNS, T cell responses
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Jin, Young-Hee

× Jin, Young-Hee

en Jin, Young-Hee

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Kaneyama, Tomoki

× Kaneyama, Tomoki

en Kaneyama, Tomoki

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Kang, Min Hyung

× Kang, Min Hyung

en Kang, Min Hyung

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Kang, Hyun Seok

× Kang, Hyun Seok

en Kang, Hyun Seok

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Koh, Chang-Sung

× Koh, Chang-Sung

en Koh, Chang-Sung

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Kim, Byung S.

× Kim, Byung S.

en Kim, Byung S.

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出版者
出版者 BIOMED CENTRAL LTD
引用
内容記述 JOURNAL OF NEUROINFLAMMATION. 8:178 (2011)
書誌情報 JOURNAL OF NEUROINFLAMMATION

巻 8, p. 178, 発行日 2011-12
抄録
内容記述 Background: We have previously shown that toll-like receptor 3 (TLR3)-mediated signaling plays an important role in the induction of innate cytokine responses to Theiler's murine encephalomyelitis virus (TMEV) infection. In addition, cytokine levels produced after TMEV infection are significantly higher in the glial cells of susceptible SJL mice compared to those of resistant C57BL/6 mice. However, it is not known whether TLR3-mediated signaling plays a protective or pathogenic role in the development of demyelinating disease. Methods: SJL/J and B6; 129S-Tlr3(tm1Flv)/J (TLR3KO-B6) mice, and TLR3KO-SJL mice that TLR3KO-B6 mice were backcrossed to SJL/J mice for 6 generations were infected with Theiler's murine encephalomyelitis virus (2 x 10(5) PFU) with or without treatment with 50 mu g of poly IC. Cytokine production and immune responses in the CNS and periphery of infected mice were analyzed. Results: We investigated the role of TLR3-mediated signaling in the protection and pathogenesis of TMEV-induced demyelinating disease. TLR3KO-B6 mice did not develop demyelinating disease although they displayed elevated viral loads in the CNS. However, TLR3KO-SJL mice displayed increased viral loads and cellular infiltration in the CNS, accompanied by exacerbated development of demyelinating disease, compared to the normal littermate mice. Late, but not early, anti-viral CD4(+) and CD8(+) T cell responses in the CNS were compromised in TLR3KO-SJL mice. However, activation of TLR3 with poly IC prior to viral infection also exacerbated disease development, whereas such activation after viral infection restrained disease development. Activation of TLR3 signaling prior to viral infection hindered the induction of protective IFN-gamma-producing CD4(+) and CD8(+) T cell populations. In contrast, activation of these signals after viral infection improved the induction of IFN-gamma-producing CD4(+) and CD8(+) T cells. In addition, poly IC-pretreated mice displayed elevated PDL-1 and regulatory FoxP3(+) CD4+ T cells in the CNS, while poly IC-post-treated mice expressed reduced levels of PDL-1 and FoxP3(+) CD4(+) T cells. Conclusions: These results suggest that TLR3-mediated signaling during viral infection protects against demyelinating disease by reducing the viral load and modulating immune responses. In contrast, premature activation of TLR3 signal transduction prior to viral infection leads to pathogenesis via over-activation of the pathogenic immune response.
資源タイプ(コンテンツの種類)
ISSN
収録物識別子タイプ PISSN
収録物識別子 1742-2094
書誌レコードID
収録物識別子タイプ NCID
収録物識別子 AA12051048
PubMed
識別子タイプ PMID
関連識別子 https://pubmed.ncbi.nlm.nih.gov/22189096
関連名称 22189096
権利
権利情報 Copyright© 2011 Jin et al; licensee BioMed Central Ltd. / This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
WoS
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000302163300001
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Cite as

Jin, Young-Hee, Kaneyama, Tomoki, Kang, Min Hyung, Kang, Hyun Seok, Koh, Chang-Sung, Kim, Byung S., 2011, TLR3 signaling is either protective or pathogenic for the development of Theiler's virus-induced demyelinating disease depending on the time of viral infection: BIOMED CENTRAL LTD, 178– p.

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