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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-1\u03b2 in human macrophages. In addition to the upregulation of pyronecrosis genes, the expressions of pyroptosis-related proteins (GSDMD, caspase-1 and IL-1\u03b2) were also elevated. To be noted, platelets were found to play a protective role in DBV-derived pyroptosis. Transcriptome analysis and <jats:italic>in vitro<\/jats:italic> 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 replication niches in human macrophages and platelets provide an additional layer to reduce cellular death. These findings may have important implications to the pathogenesis of lethal DBV, and provide new ideas for developing novel therapeutics to combat its infection.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011488","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T17:29:56Z","timestamp":1690219796000},"page":"e0011488","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dabie bandavirus infection induces macrophagic pyroptosis and this process is attenuated by 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