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

Abstract

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.