Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure

• DOI: 10.1016/j.celrep.2025.115479
• Publication Date: 2025-04-01T02:15:35Z
• Authors: Yan Zhang; Guoying Zhang; Brittany Dong; Ankit Pandeya; Jian Cui; Samuel dos Santos...; Ling Yang; Jiaqian Qi; Zhuodong Chai; Congqing Wu; Daniel Kirchhofer; Toshihiko Shiroishi; Fadi Khasawneh; Min Tao; Feng Shao; Christopher M. Wa...; Yinan Wei; Zhenyu Li
• Keywords: Pyroptosis; NLRC4; efferocytosis

Highlights•Activation of the NAIP/NLRC4 inflammasome triggers acute lung injury in mice•NAIP/NLRC4 components are expressed macrophages and pulmonary fibroblasts•Acute caused by activation is dependent on pyroptosis•Pyroptosis both fibroblasts contributes to injurySummaryThe plays a pivotal role defense against bacterial infections, with its vivo physiological function primarily recognized as driving inflammation immune cells. Acute (ALI) leading cause mortality sepsis. In this study, we identify that highly pyroptosis these cells critical injury. Mice challenged gram-negative bacteria or flagellin developed lethal injury, characterized reduced blood oxygen saturation, disrupted barrier function, escalated inflammation. Flagellin-induced was protected caspase-1 GSDMD-deficient mice. These findings enhance our understanding inflammasome's (patho)physiological highlight significant ALI during sepsis.Graphical abstract