國家衛生研究院 NHRI:Item 3990099045/11220
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    題名: Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells
    作者: Lai, JH;Wang, MY;Huang, CY;Wu, CH;Hung, LF;Yang, CY;Ke, PY;Luo, SF;Liu, SJ;Ho, LJ
    貢獻者: National Institute of Infectious Diseases and Vaccinology;Institute of Cellular and Systems Medicine
    摘要: Toll-like receptors (TLRs) are important sensors that recognize pathogen-associated molecular patterns. Generally, TLR9 is known to recognize bacterial or viral DNA but not viral RNA and initiate an immune response. Herein, we demonstrate that infection with dengue virus (DENV), an RNA virus, activates TLR9 in human dendritic cells (DCs). DENV infection induces release of mitochondrial DNA (mtDNA) into the cytosol and activates TLR9 signaling pathways, leading to production of interferons (IFNs). The DENV-induced mtDNA release involves reactive oxygen species generation and inflammasome activation. DENV infection disrupts the association between transcription factor A mitochondria (TFAM) and mtDNA and activates the mitochondrial permeability transition pores. The side-by-side comparison of TLR9 and cyclic GMP-AMP synthase (cGAS) knockdown reveals that both cGAS and TLR9 comparably contribute to DENV-induced immune activation. The significance of TLR9 in DENV-induced immune response is also confirmed in examination with the bone marrow-derived DCs prepared from Tlr9-knockout mice. Our study unravels a previously unrecognized phenomenon in which infection with an RNA virus, DENV, activates TLR9 signaling by inducing mtDNA release in human DCs.
    日期: 2018-08
    關聯: EMBO Reports. 2018 Aug;19(8):Article number e46182.
    Link to: http://dx.doi.org/10.15252/embr.201846182
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1469-221X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000440648700012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85051069987
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