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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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028086 |
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| Summary: | 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. |
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| ISSN: | 2589-0042 |