Cytosolic mtDNA released from pneumolysin-damaged mitochondria triggers IFN-β production in epithelial cells
Cytosolic mtDNA released from pneumolysin-damaged mitochondria triggers IFN-β production in epithelial cells
复制标题
从肺炎球菌溶血素损伤的线粒体释放的胞质 mtDNA 触发上皮细胞中 IFN-β 的产生
DOI：
10.1139/cjm-2019-0481
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Hong Wang
中科院分区：
文献类型：
--
作者：
Yuting Fang;Xuemei Zhang;Chang Lu;Yibing Yin;Xuexue Hu;Wenchun Xu;Yusi Liu;Hong Wang
肺炎链球菌溶血素（Ply）是肺炎链球菌的主要毒力因子。Ply诱导的宿主巨噬细胞中的干扰素-β（IFN-β）表达已被证明是由于在S.肺炎感染我们的研究结果扩展了这项工作，表明位于炎症损伤界面的人支气管上皮细胞BEAS-2B通过改变线粒体状态和释放过量的mtDNA来适应局部线索。本研究结果表明，纯化的Ply在体内和体外均可诱导人上皮细胞表达IFN-β，并伴有线粒体损伤。感染S.肺炎。总之，我们的研究表明，Ply触发上皮细胞中IFN-β的产生，并且这种反应是由Ply损伤的线粒体释放的mtDNA介导的。它显示了IFN-β对S的显著调节作用。上皮细胞内肺炎。
Pneumolysin (Ply) is a major virulence factor ofStreptococcus pneumoniae. Ply-induced interferon-β (IFN-β) expression in host macrophages has been shown to be due to the accumulation of mitochondrial deoxyribonucleic acid (mtDNA) in the cytoplasm duringS. pneumoniaeinfection. Our findings extend this work to show human bronchial epithelial cells that reside at the interface of inflammatory injury, BEAS-2B, adapt to local cues by altering mitochondrial states and releasing excess mtDNA. The results in this research showed that purified Ply induced the expression of IFN-β in human epithelial cells, which was accompanied by mitochondrial damage both in vivo and in vitro. The observations also were supported by the increased mtDNA concentrations in the bronchial lavage fluid of mice infected withS. pneumoniae. In summary, our study demonstrated that Ply triggered the production of IFN-β in epithelial cells, and this response was mediated by mtDNA released from Ply-damaged mitochondria. It displayed an impressive modulation of IFN-β response toS. pneumoniaein epithelial cells.