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. 2024 Dec 12;28(1):111581.
doi: 10.1016/j.isci.2024.111581. eCollection 2025 Jan 17. TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells
Yuling Sun 1 , Huidi Yu 1 , Zhihao Zhan 1 , Wei Liu 1 , Penggang Liu 1 , Jing Sun 1 , Pinghu Zhang 2 , Xiaoquan Wang 3 4 , Xiufan Liu 3 4 , Xiulong Xu 1 4
Affiliations
Pyroptosis plays an important role in attracting innate immune cells to eliminate infected niches. Our study focuses on how influenza A virus (IAV) infection triggers pyroptosis in respiratory epithelial cells. Here, we report that IAV infection induces pyroptosis in a human and murine airway epithelial cell line. Mechanistically, IAV infection activates caspase-8 and caspase-3, which cleave and activate gasdermin (GSDM) D and GSDME, respectively. Z-nucleic acid-binding protein 1 (ZBP1) and receptor-interacting protein kinase (RIPK) 1 activity but not RIPK3 are required for caspase-8/3 and GSDMD/E activation and pyroptosis. GSDMD/E, ZBP1, and RIPK1 knockout all block IAV-induced pyroptosis but enhance virus replication. Transforming growth factor β-activated kinase 1 (TAK1) activation via the adaptor protein TRIF suppresses RIPK1, caspase-8/3, and GSDMD/E activation and pyroptosis. The TAK1 inhibitor 5Z-oxzeneonal (5Z) enhances IAV-induced caspase-8/3 and GSDMD/E cleavage in the lung tissues of IAV-infected mice. Our study unveils a previously unrecognized mechanism of regulation of IAV-induced pyroptosis in respiratory epithelial cells.
Keywords: cell biology; integrative aspects of cell biology; model organism; molecular network; virology.
. 2024 Dec 12;28(1):111581.
doi: 10.1016/j.isci.2024.111581. eCollection 2025 Jan 17. TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells
Yuling Sun 1 , Huidi Yu 1 , Zhihao Zhan 1 , Wei Liu 1 , Penggang Liu 1 , Jing Sun 1 , Pinghu Zhang 2 , Xiaoquan Wang 3 4 , Xiufan Liu 3 4 , Xiulong Xu 1 4
Affiliations
- PMID: 39811662
- PMCID: PMC11732511
- DOI: 10.1016/j.isci.2024.111581
Pyroptosis plays an important role in attracting innate immune cells to eliminate infected niches. Our study focuses on how influenza A virus (IAV) infection triggers pyroptosis in respiratory epithelial cells. Here, we report that IAV infection induces pyroptosis in a human and murine airway epithelial cell line. Mechanistically, IAV infection activates caspase-8 and caspase-3, which cleave and activate gasdermin (GSDM) D and GSDME, respectively. Z-nucleic acid-binding protein 1 (ZBP1) and receptor-interacting protein kinase (RIPK) 1 activity but not RIPK3 are required for caspase-8/3 and GSDMD/E activation and pyroptosis. GSDMD/E, ZBP1, and RIPK1 knockout all block IAV-induced pyroptosis but enhance virus replication. Transforming growth factor β-activated kinase 1 (TAK1) activation via the adaptor protein TRIF suppresses RIPK1, caspase-8/3, and GSDMD/E activation and pyroptosis. The TAK1 inhibitor 5Z-oxzeneonal (5Z) enhances IAV-induced caspase-8/3 and GSDMD/E cleavage in the lung tissues of IAV-infected mice. Our study unveils a previously unrecognized mechanism of regulation of IAV-induced pyroptosis in respiratory epithelial cells.
Keywords: cell biology; integrative aspects of cell biology; model organism; molecular network; virology.