https://scholars.lib.ntu.edu.tw/handle/123456789/340530
標題: | CLEC5A is critical for dengue-virus-induced lethal disease | 作者: | CHIEN-KUO LEE Chen, Szu-Ting Lin, Yi-Ling Huang, Ming-Ting Wu, Ming-Fang Cheng, Shih-Chin Lei, Huan-Yao Lee, Chien-Kuo Chiou, Tzyy-Wen Wong, Chi-Huey Hsieh, Shie-Liang |
公開日期: | 2008 | 卷: | 453 | 期: | 7195 | 起(迄)頁: | 672-676 | 來源出版物: | Nature | 摘要: | Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts. CLEC5A (C-type lectin domain family 5, member A; also known as myeloid DAP12-associating lectin (MDL-1)) contains a C-type lectin-like fold similar to the natural-killer T-cell C-type lectin domains and associates with a 12-kDa DNAX-activating protein (DAP12) on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation. The CLEC5A-DV interaction does not result in viral entry but stimulates the release of proinflammatory cytokines. Blockade of CLEC5A-DV interaction suppresses the secretion of proinflammatory cytokines without affecting the release of interferon-α, supporting the notion that CLEC5A acts as a signalling receptor for proinflammatory cytokine release. Moreover, anti-CLEC5A monoclonal antibodies inhibit DV-induced plasma leakage, as well as subcutaneous and vital-organ haemorrhaging, and reduce the mortality of DV infection by about 50% in STAT1-deficient mice. Our observation that blockade of CLEC5A-mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with DV (either alone or complexed with an enhancing antibody) offers a promising strategy for alleviating tissue damage and increasing the survival of patients suffering from dengue haemorrhagic fever and dengue shock syndrome, and possibly even other virus-induced inflammatory diseases. ?2008 Nature Publishing Group. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-44449097101&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/340530 |
DOI: | 10.1038/nature07013 | SDG/關鍵字: | alpha interferon; killer cell activating receptor associated protein; lectin; monoclonal antibody; protein clec5a; STAT1 protein; tumor necrosis factor alpha; antibody; blood; dengue fever; protein; rodent; virus; animal experiment; animal model; article; controlled study; cytokine release; dengue; Dengue virus; enzyme linked immunosorbent assay; intestinal bleeding; mouse; nonhuman; priority journal; protein interaction; protein phosphorylation; virion; virus replication; Western blotting; Dengue virus; Mus |
顯示於: | 免疫學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。