CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages

Ming Fang Wu, Szu Ting Chen, An Hang Yang, Wan Wan Lin, Yi Ling Lin, Nien Jung Chen, I. Shuen Tsai, Lei Li, Shie Liang Hsieh*

*此作品的通信作者

研究成果: Article同行評審

165 引文 斯高帕斯(Scopus)

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.

原文English
頁(從 - 到)95-106
頁數12
期刊Blood
121
發行號1
DOIs
出版狀態Published - 3 1月 2013

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