Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection
Abstract Neutrophils and macrophages are critical for antiviral immunity, but their reciprocal regulatory roles and mechanisms in the response to viral infection remain unclear. Herein, we found that the ion channel Piezo1 directs neutrophil extracellular trap (NET) formation and regulates macrophag...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07395-5 |
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| author | Yuexin Wang Qiuli Yang Yingjie Dong Likun Wang Zhiyuan Zhang Ruiying Niu Yufei Wang Yujing Bi Guangwei Liu |
| author_facet | Yuexin Wang Qiuli Yang Yingjie Dong Likun Wang Zhiyuan Zhang Ruiying Niu Yufei Wang Yujing Bi Guangwei Liu |
| author_sort | Yuexin Wang |
| collection | DOAJ |
| description | Abstract Neutrophils and macrophages are critical for antiviral immunity, but their reciprocal regulatory roles and mechanisms in the response to viral infection remain unclear. Herein, we found that the ion channel Piezo1 directs neutrophil extracellular trap (NET) formation and regulates macrophage functional differentiation in anti-influenza virus immunity. Genetic deletion of Piezo1 in neutrophils inhibited the generation of NETs and M1 macrophage differentiation while driving the development of M2 macrophages during viral infection. Piezo1-directed neutrophil NET DNA directly regulates macrophage differentiation in vitro and in vivo. Mechanistically, neutrophil Piezo1 deficiency inhibited NET DNA production, leading to decreased TLR9 and cGAS-STING signalling activity while inducing reciprocal differentiation from M1 to M2 macrophages. In addition, Piezo1 integrates magnesium signalling and the SIRT2-hypoxia-inducible factor-1 alpha (HIF1α)-dependent pathway to orchestrate reciprocal M1 and M2 macrophage lineage commitment through neutrophil-derived NET DNA. Our studies provide critical insight into the role of neutrophil-based mechanical regulation of immunopathology in directing macrophage lineage commitment during the response to influenza virus infection. |
| format | Article |
| id | doaj-art-a69b332e45bb40ce85155bbd5f3facd6 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-a69b332e45bb40ce85155bbd5f3facd62025-02-02T12:44:49ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111310.1038/s41419-025-07395-5Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infectionYuexin Wang0Qiuli Yang1Yingjie Dong2Likun Wang3Zhiyuan Zhang4Ruiying Niu5Yufei Wang6Yujing Bi7Guangwei Liu8Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical ScienceKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical ScienceKey Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal UniversityAbstract Neutrophils and macrophages are critical for antiviral immunity, but their reciprocal regulatory roles and mechanisms in the response to viral infection remain unclear. Herein, we found that the ion channel Piezo1 directs neutrophil extracellular trap (NET) formation and regulates macrophage functional differentiation in anti-influenza virus immunity. Genetic deletion of Piezo1 in neutrophils inhibited the generation of NETs and M1 macrophage differentiation while driving the development of M2 macrophages during viral infection. Piezo1-directed neutrophil NET DNA directly regulates macrophage differentiation in vitro and in vivo. Mechanistically, neutrophil Piezo1 deficiency inhibited NET DNA production, leading to decreased TLR9 and cGAS-STING signalling activity while inducing reciprocal differentiation from M1 to M2 macrophages. In addition, Piezo1 integrates magnesium signalling and the SIRT2-hypoxia-inducible factor-1 alpha (HIF1α)-dependent pathway to orchestrate reciprocal M1 and M2 macrophage lineage commitment through neutrophil-derived NET DNA. Our studies provide critical insight into the role of neutrophil-based mechanical regulation of immunopathology in directing macrophage lineage commitment during the response to influenza virus infection.https://doi.org/10.1038/s41419-025-07395-5 |
| spellingShingle | Yuexin Wang Qiuli Yang Yingjie Dong Likun Wang Zhiyuan Zhang Ruiying Niu Yufei Wang Yujing Bi Guangwei Liu Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection Cell Death and Disease |
| title | Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection |
| title_full | Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection |
| title_fullStr | Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection |
| title_full_unstemmed | Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection |
| title_short | Piezo1-directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection |
| title_sort | piezo1 directed neutrophil extracellular traps regulate macrophage differentiation during influenza virus infection |
| url | https://doi.org/10.1038/s41419-025-07395-5 |
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