TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells
Summary: 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 airw...
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Elsevier
2025-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028086 |
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| author | Yuling Sun Huidi Yu Zhihao Zhan Wei Liu Penggang Liu Jing Sun Pinghu Zhang Xiaoquan Wang Xiufan Liu Xiulong Xu |
| author_facet | Yuling Sun Huidi Yu Zhihao Zhan Wei Liu Penggang Liu Jing Sun Pinghu Zhang Xiaoquan Wang Xiufan Liu Xiulong Xu |
| author_sort | Yuling Sun |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-26ec88d3a15b49b7a97609ddfc4de1d4 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-26ec88d3a15b49b7a97609ddfc4de1d42024-12-26T08:57:23ZengElsevieriScience2589-00422025-01-01281111581TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cellsYuling Sun0Huidi Yu1Zhihao Zhan2Wei Liu3Penggang Liu4Jing Sun5Pinghu Zhang6Xiaoquan Wang7Xiufan Liu8Xiulong Xu9College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. ChinaInstitute of Translational Medicine, Yangzhou University Medical College, Yangzhou 225009, Jiangsu Province, P.R. ChinaAnimal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, Jiangsu Province, ChinaAnimal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, Jiangsu Province, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, Jiangsu Province, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224028086molecular networkvirologycell biologyintegrative aspects of cell biologymodel organism |
| spellingShingle | Yuling Sun Huidi Yu Zhihao Zhan Wei Liu Penggang Liu Jing Sun Pinghu Zhang Xiaoquan Wang Xiufan Liu Xiulong Xu TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells iScience molecular network virology cell biology integrative aspects of cell biology model organism |
| title | TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells |
| title_full | TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells |
| title_fullStr | TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells |
| title_full_unstemmed | TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells |
| title_short | TRIF-TAK1 signaling suppresses caspase-8/3-mediated GSDMD/E activation and pyroptosis in influenza A virus-infected airway epithelial cells |
| title_sort | trif tak1 signaling suppresses caspase 8 3 mediated gsdmd e activation and pyroptosis in influenza a virus infected airway epithelial cells |
| topic | molecular network virology cell biology integrative aspects of cell biology model organism |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028086 |
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