Exosome-mediated modulation of macrophage polarization and inflammation in early Klebsiella pneumoniae lung infections.

Klebsiella pneumoniae is a major pathogen responsible for severe pulmonary infections, yet the early mechanisms of infection remain incompletely understood. This study investigates the role of exosomes derived from K. pneumoniae in polarizing macrophages to the M1 phenotype, thereby facilitating early lung infections. Utilizing single-cell Raman spectroscopy, we rapidly detected K. pneumoniae within host cells and observed significant lipid expression changes. Metabolomic analysis of exosomes from infected epithelial cells uncovered an elevation of phosphatidylcholine, which disrupted endothelial tight junctions and promoted M1 macrophage recruitment and polarization. This process activated the NF-κB signaling pathway, increasing inflammatory responses and attracting neutrophils. Our findings, validated in infected tissue models, suggest that these exosomal mechanisms significantly contribute to the early stages of pulmonary infection by K. pneumoniae. This study offers crucial insights into potential therapeutic targets for controlling K. pneumoniae infections.