Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure
Summary: The NAIP/NLRC4 inflammasome plays a pivotal role in the defense against bacterial infections, with its in vivo physiological function primarily recognized as driving inflammation in immune cells. Acute lung injury (ALI) is a leading cause of mortality in sepsis. In this study, we identify t...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725002505 |
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| author | Yan Zhang Guoying Zhang Brittany Dong Ankit Pandeya Jian Cui Samuel dos Santos Valenca Ling Yang Jiaqian Qi Zhuodong Chai Congqing Wu Daniel Kirchhofer Toshihiko Shiroishi Fadi Khasawneh Min Tao Feng Shao Christopher M. Waters Yinan Wei Zhenyu Li |
| author_facet | Yan Zhang Guoying Zhang Brittany Dong Ankit Pandeya Jian Cui Samuel dos Santos Valenca Ling Yang Jiaqian Qi Zhuodong Chai Congqing Wu Daniel Kirchhofer Toshihiko Shiroishi Fadi Khasawneh Min Tao Feng Shao Christopher M. Waters Yinan Wei Zhenyu Li |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | Summary: The NAIP/NLRC4 inflammasome plays a pivotal role in the defense against bacterial infections, with its in vivo physiological function primarily recognized as driving inflammation in immune cells. Acute lung injury (ALI) is a leading cause of mortality in sepsis. In this study, we identify that the NAIP/NLRC4 inflammasome is highly expressed in both macrophages and pulmonary fibroblasts and that pyroptosis of these cells plays a critical role in lung injury. Mice challenged with gram-negative bacteria or flagellin developed lethal lung injury, characterized by reduced blood oxygen saturation, disrupted lung barrier function, and escalated inflammation. Flagellin-induced lung injury was protected in caspase-1 or GSDMD-deficient mice. These findings enhance our understanding of the NAIP/NLRC4 inflammasome’s (patho)physiological function and highlight the significant role of inflammasome activation and pyroptosis in ALI during sepsis. |
| format | Article |
| id | doaj-art-4199f492bf8d4caa88807ef1a7755be6 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-4199f492bf8d4caa88807ef1a7755be62025-08-20T02:10:23ZengElsevierCell Reports2211-12472025-04-0144411547910.1016/j.celrep.2025.115479Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failureYan Zhang0Guoying Zhang1Brittany Dong2Ankit Pandeya3Jian Cui4Samuel dos Santos Valenca5Ling Yang6Jiaqian Qi7Zhuodong Chai8Congqing Wu9Daniel Kirchhofer10Toshihiko Shiroishi11Fadi Khasawneh12Min Tao13Feng Shao14Christopher M. Waters15Yinan Wei16Zhenyu Li17Department of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USA; Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USADepartment of Physiology, University of Kentucky, Lexington, KY 40506, USADepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USA; Department of Chemistry, University of Kentucky, Lexington, KY 40506, USADepartment of Chemistry, University of Kentucky, Lexington, KY 40506, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40506, USADepartment of Physiology, University of Kentucky, Lexington, KY 40506, USADepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USADepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USADepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USASaha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40506, USA; Department of Surgery, University of Kentucky, Lexington, KY 40506, USADepartment of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USARIKEN BioResource Research Center, Tsukuba, Ibaraki 305-0074, JapanDepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USADepartment of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaNational Institute of Biological Sciences, Beijing 102206 ChinaDepartment of Physiology, University of Kentucky, Lexington, KY 40506, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40506, USADepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USADepartment of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USA; Corresponding authorSummary: The NAIP/NLRC4 inflammasome plays a pivotal role in the defense against bacterial infections, with its in vivo physiological function primarily recognized as driving inflammation in immune cells. Acute lung injury (ALI) is a leading cause of mortality in sepsis. In this study, we identify that the NAIP/NLRC4 inflammasome is highly expressed in both macrophages and pulmonary fibroblasts and that pyroptosis of these cells plays a critical role in lung injury. Mice challenged with gram-negative bacteria or flagellin developed lethal lung injury, characterized by reduced blood oxygen saturation, disrupted lung barrier function, and escalated inflammation. Flagellin-induced lung injury was protected in caspase-1 or GSDMD-deficient mice. These findings enhance our understanding of the NAIP/NLRC4 inflammasome’s (patho)physiological function and highlight the significant role of inflammasome activation and pyroptosis in ALI during sepsis.http://www.sciencedirect.com/science/article/pii/S2211124725002505CP: Immunology |
| spellingShingle | Yan Zhang Guoying Zhang Brittany Dong Ankit Pandeya Jian Cui Samuel dos Santos Valenca Ling Yang Jiaqian Qi Zhuodong Chai Congqing Wu Daniel Kirchhofer Toshihiko Shiroishi Fadi Khasawneh Min Tao Feng Shao Christopher M. Waters Yinan Wei Zhenyu Li Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure Cell Reports CP: Immunology |
| title | Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure |
| title_full | Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure |
| title_fullStr | Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure |
| title_full_unstemmed | Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure |
| title_short | Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure |
| title_sort | pyroptosis of pulmonary fibroblasts and macrophages through nlrc4 inflammasome leads to acute respiratory failure |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725002505 |
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