https://scholars.lib.ntu.edu.tw/handle/123456789/550452
標題: | CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages | 作者: | Wu M.-F. Chen S.-T. Yang A.-H. WAN-WAN LIN Lin Y.-L. Chen N.-J. Tsai I.-S. Li L. Hsieh S.-L. |
公開日期: | 2013 | 卷: | 121 | 期: | 1 | 起(迄)頁: | 95-106 | 來源出版物: | Blood | 摘要: | Persistent high fever is one of the most typical clinical symptoms in dengue virus (DV)-infected patients. However, the source of endogenous pyrogen (eg, IL-1β) and the signaling cascade leading to the activation of inflammasome and caspase-1, which are essential for IL-1β and IL-18 secretion, during dengue infection have not been elucidated yet. Macrophages can be polarized into distinct phenotypes under the influence of GM-CSF or M-CSF, denoted as GM-MΦ and M-MΦ, respectively. We found that DV induced high levels of IL-1β and IL-18 from GM-MΦ (inflammatory macrophage) and caused cell death (pyroptosis), whereas M-MΦ (resting macrophage) did not produce IL-1β and IL-18 on DV infection even with lipopolysaccharide priming. This observation demonstrates the distinct responses of GM-MΦ and M-MΦ to DV infection. Moreover, up-regulation of pro-IL-1β, pro-IL-18, and NLRP3 associated with caspase-1 activation was observed in DV-infected GM-MΦ, whereas blockade of CLEC5A/MDL-1, a C-type lectin critical for dengue hemorrhagic fever and Japanese encephalitis virus infection, inhibits NLRP3 inflammasome activation and pyrotopsis in GM-MΦ. Thus, DV can activate NLRP3 inflammasome via CLEC5A, and GM-MΦ plays a more important role than M-MΦ in the pathogenesis of DV infection. ? 2013 by The American Society of Hematology. |
URI: | 2-s2.0-84872057098 https://scholars.lib.ntu.edu.tw/handle/123456789/550452 |
ISSN: | 64971 | DOI: | 10.1182/blood-2012-05-430090 | SDG/關鍵字: | C type lectin 5A; cryopyrin; inflammasome; interleukin 18; interleukin 1beta; interleukin 1beta converting enzyme; lectin; unclassified drug; apoptosis; article; cell level; controlled study; cytokine response; dengue; Dengue virus; enzyme activation; human; human cell; intracellular signaling; macrophage activation; priority journal; pyroptosis; upregulation; virus pathogenesis |
顯示於: | 藥理學科所 |
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