Dabie bandavirus infection induces macrophagic pyroptosis and this process is attenuated by platelets

作者：Sicong Yu, Qinyi Zhang, Lingxuan Su, Ji He, Wen Shi, Hao Yan, Haiyan Mao, Yi Sun, Dongqing Cheng, Xuan Wang, Yanjun Zhang, Lei Fang · 发表于：PLoS neglected tropical diseases · 年份：2023 · DOI：10.1371/journal.pntd.0011488 · 被引用次数：12 · 研究领域：Viral Infections and Vectors、Inflammasome and immune disorders、Mosquito-borne diseases and control

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high mortality rate in humans, which is caused by Dabie bandavirus (DBV), formerly known as SFTS virus. Clinical manifestations of SFTS are characterized by high fever, thrombocytopenia, leukopenia, hemorrhage, gastrointestinal symptoms, myalgia and local lymph node enlargement with up to 30% case fatality rates in human. Macrophage depletion in secondary lymphoid organs have important roles in the pathogenic process of fatal SFTS, but its exact cell death mechanism remains largely unknown. Here, we showed for the first time that DBV infection induced macrophagic pyroptosis, as evidenced by swollen cells, pore-forming structures, accumulation of gasdermin D N-terminal (GSDMD-NT) as well as the release of lactate dehydrogenase (LDH) and IL-1β in human macrophages. In addition to the upregulation of pyronecrosis genes, the expressions of pyroptosis-related proteins (GSDMD, caspase-1 and IL-1β) were also elevated. To be noted, platelets were found to play a protective role in DBV-derived pyroptosis. Transcriptome analysis and in vitro studies demonstrated that platelets significantly reduced the gene expressions and protein production of pro-pyroptotic markers and inflammatory cytokines in macrophages, whereas platelets conferred a propagation advantage for DBV. Collectively, this study demonstrates a novel mechanism by which DBV invasion triggers pyroptosis as a host defense to remove ...