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
Department of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USA; Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Pharmaceutical Sciences, Texas A&M University, College Station, TX 77843, USA.
Cell Rep. 2025 Apr 22;44(4):115479. doi: 10.1016/j.celrep.2025.115479. Epub 2025 Mar 29.
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.
NAIP/NLRC4炎性小体在抵御细菌感染中起关键作用，其体内生理功能主要被认为是驱动免疫细胞中的炎症反应。急性肺损伤（ALI）是脓毒症患者死亡的主要原因。在本研究中，我们发现NAIP/NLRC4炎性小体在巨噬细胞和肺成纤维细胞中均高表达，且这些细胞的焦亡在肺损伤中起关键作用。用革兰氏阴性菌或鞭毛蛋白攻击的小鼠会发生致命性肺损伤，其特征为血氧饱和度降低、肺屏障功能破坏和炎症加剧。在caspase-1或GSDMD缺陷的小鼠中，鞭毛蛋白诱导的肺损伤得到了保护。这些发现加深了我们对NAIP/NLRC4炎性小体（病理）生理功能的理解，并突出了炎性小体激活和焦亡在脓毒症期间ALI中的重要作用。
