國家衛生研究院 NHRI:Item 3990099045/9880
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    題名: Dengue virus infection induces interferon-lambda1 to facilitate cell migration
    作者: Hsu, YL;Wang, MY;Ho, LJ;Lai, JH
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-lambda), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated. In the present study, we show that DENV infection preferentially induced production of IFN-lambda1 in human dendritic cells (DCs) and human lung epithelial cells. Virus nonstructural 1 (NS1) glycoprotein was responsible for the effect. DENV-induced production of IFN-lambda1 was dependent on signaling pathways involving toll-like receptor (TLR)-3, interferon regulation factor (IRF)-3, and nuclear factor-kappaB (NF-kappaB). Blocking interaction between IFN-lambda1 and its receptor IFN-lambdaR1 through siRNA interference reduced DENV-induced DC migration towards the chemoattractants CCL19 and CCL21, by inhibiting CCR7 expression. Furthermore, IFN-lambda1 itself induced CCR7 expression and DC migration. Our study presents the first evidence of the mechanisms and effects of IFN-lambda1 induction in DENV-infected DCs and highlights the role of this cytokine in the immunopathogenesis of DENV infection.
    日期: 2016-07-26
    關聯: Scientific Reports. 2016 Jul 26;6:Article number 24530.
    Link to: http://dx.doi.org/10.1038/srep24530
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000380198100001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84979516774
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