High-alcohol-producing Klebsiella pneumoniae aggravates lung injury by affecting neutrophils and the airway epithelium

作者：Jinghua Cui, Ziying Xu, Zihui Yu, Qun Zhang, Shiyu Liu, Bing Du, Lin Gan, Chao Yan, Guanhua Xue, Junxia Feng, Zheng Fan, Tongtong Fu, Yanling Feng, Hanqing Zhao, Zanbo Ding, Xiaoran Li, Rui Zhang, Xiaohu Cui, Ziyan Tian, Kewu Huang, Wenjun Wang, Yu Bai, Haijian Zhou, Ying Sun, Xiaopeng Yang, Meng Wan, Yuehua Ke, Jing Yuan · 发表于：Cell Reports Medicine · 年份：2025 · DOI：10.1016/j.xcrm.2024.101886 · 被引用次数：11 · 研究领域：Alcohol Consumption and Health Effects、Heme Oxygenase-1 and Carbon Monoxide、Advanced Glycation End Products research

We have previously reported that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut can cause endo-alcoholic fatty liver disease. Here, we discover that 91.2% of Kpn isolates from pulmonary disease samples also produce excess ethanol, which may be associated with respiratory disease severity. To further explore the potential mechanism, a murine model is established with high-dose bacteria. Kpn stimulates granular neutrophils (G0), subsequently transforming them into phagocytic neutrophils (G1). HiAlc Kpn also causes dysfunction of pyrimidine metabolism, leading to neutrophil apoptosis. These changes inhibit phagocytosis of neutrophils and possibly suppress inflammasome-dependent innate immunity. In a persistent infective murine model, HiAlc Kpn induces lung fibrosis and production of reactive oxygen species (ROS), possibly affecting epithelial cell apoptosis and lung function. The results suggest that the subtype of neutrophil is a potential biomarker for the severity of lung injury caused by HiAlc Kpn.