Cell reports · 2025
Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure.
СтатьяНазвание и аннотация: Перевод в очереди
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Zhang Yan, Zhang Guoying, Dong Brittany, Pandeya Ankit, Cui Jian, Valenca Samuel Dos Santos, Yang Ling, Qi Jiaqian, Chai Zhuodong, Wu Congqing, Kirchhofer Daniel, Shiroishi Toshihiko, Khasawneh Fadi, Tao Min, Shao Feng, Waters Christopher M, Wei Yinan, Li Zhenyu
Аннотация
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.