Exosome-mediated modulation of macrophage polarization and inflammation in early <i>Klebsiella pneumoniae</i> 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.
Authors
- Shanyu Li
- Shouyue Liu
- Yanan Li
- Ziyu Liu
- Ying Xue
- Ping Ren
- Ying Zhang
Institutions
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Changchun Children's Hospital (CN)
- Second Affiliated Hospital of Jilin University (CN)
- IS Instruments (United Kingdom) (GB)
Publication Details
- Journal
- Clinical Science
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1042/cs20256616
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Natural Science Foundation of Jilin Province
- Jilin Province Development and Reform Commission
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- People's Government of Jilin Province
- National Development and Reform Commission
- National Postdoctoral Program for Innovative Talents