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| Poly(I:C) Induces Antiviral Immune Responses in Japanese Flounder (Paralichthys olivaceus) That Require TLR3 and MDA5 and Is Negatively Regulated by Myd88 | |
| Zhou, Zhi-xia1; Zhang, Bao-cun1,2; Sun, Li1,3; Sun, L (reprint author), Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China. | |
| 2014-11-13 | |
| 发表期刊 | PLOS ONE
 |
| 卷号 | 9期号:11页码:e112918 |
| 文章类型 | Article |
| 摘要 | Polyinosinic:polycytidylic acid (poly(I:C)) is a ligand of toll-like receptor (TLR) 3 that has been used as an immunostimulant in humans and mice against viral diseases based on its ability to enhance innate and adapt immunity. Antiviral effect of poly(I:C) has also been observed in teleost, however, the underling mechanism is not clear. In this study, we investigated the potential and signaling mechanism of poly(I:C) as an antiviral agent in a model of Japanese flounder (Paralichthys olivaceus) infected with megalocytivirus. We found that poly(I:C) exhibited strong antiviral activity and enhanced activation of head kidney macrophages and peripheral blood leukocytes. In vivo studies showed that (i) TLR3 as well as MDA5 knockdown reduced poly(I:C)-mediated immune response and antiviral activity to significant extents; (ii) when Myd88 was overexpressed in flounder, poly(I:C)-mediated antiviral activity was significantly decreased; (iii) when Myd88 was inactivated, the antiviral effect of poly(I:C) was significantly increased. Cellular study showed that (i) the NF-kappa B activity induced by poly(I:C) was upregulated in Myd88-overexpressing cells and unaffected in Myd88-inactivated cells; (ii) Myd88 overexpression inhibited and upregulated the expression of poly(I:C)-induced antiviral genes and inflammatory genes respectively; (iii) Myd88 inactivation enhanced the expression of the antiviral genes induced by poly(I:C). Taken together, these results indicate that poly(I:C) is an immunostimulant with antiviral potential, and that the immune response of poly(I:C) requires TLR3 and MDA5 and is negatively regulated by Myd88 in a manner not involving NK-kappa B. These results provide insights to the working mechanism of poly(I:C), TLR3, and Myd88 in fish. |
| 学科领域 | Science & Technology - Other Topics |
| DOI | 10.1371/journal.pone.0112918 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000347709300122 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/24146 |
| 专题 | 实验海洋生物学重点实验室 |
| 通讯作者 | Sun, L (reprint author), Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China. |
| 作者单位 | 1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Zhejiang Univ, Collaborat Innovat Ctr Deep Sea Biol, Hangzhou 310003, Zhejiang, Peoples R China |
| 第一作者单位 | 中国科学院海洋研究所 |
| 推荐引用方式 GB/T 7714 | Zhou, Zhi-xia,Zhang, Bao-cun,Sun, Li,et al. Poly(I:C) Induces Antiviral Immune Responses in Japanese Flounder (Paralichthys olivaceus) That Require TLR3 and MDA5 and Is Negatively Regulated by Myd88[J]. PLOS ONE,2014,9(11):e112918. |
| APA | Zhou, Zhi-xia,Zhang, Bao-cun,Sun, Li,&Sun, L .(2014).Poly(I:C) Induces Antiviral Immune Responses in Japanese Flounder (Paralichthys olivaceus) That Require TLR3 and MDA5 and Is Negatively Regulated by Myd88.PLOS ONE,9(11),e112918. |
| MLA | Zhou, Zhi-xia,et al."Poly(I:C) Induces Antiviral Immune Responses in Japanese Flounder (Paralichthys olivaceus) That Require TLR3 and MDA5 and Is Negatively Regulated by Myd88".PLOS ONE 9.11(2014):e112918. |
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