NK cell-derived exosomes improved lung injury in mouse model of Pseudomonas aeruginosa lung infection

Abstract

Background: Pseudomonas aeruginosa (PA) is one of the most common bacteria that causes lung infection in hospital. The aim of our study is to explore the role and action mechanism of NK cells in lung PA infection. Methods: In this present study, 2.5 × 108 CFU/mouse PA was injected into murine trachea to make lung PA infection mouse model. Anti-asialo GM1 was used to inhibit NK cell. The percentage of NK cells was ensured by flow cytometry, and the M1- and M2-polarized macrophages were determined by flow cytometry, qRT-PCR, and ELISA assay. Besides, H&E staining was performed to ensure the pathological changes in lung tissues. Transmission electron microscopy and western blot were carried out to identify the exosome. Results: Here, in the mouse model of PA lung infection, NK cell depletion caused M2 polarization of lung macrophage, and exacerbated PA-induced lung injury. Next, our data shown that M2 macrophage polarization was enhanced when the generation of NK cell-derived exosome was blocked in the co-culture system of NK cells and macrophages. Subsequently, we demonstrated that NK cells promoted M1 macrophage polarization both in PA-infected macrophage and the mouse model of PA lung infection, and attenuated lung injury through exosome. Conclusion: Overall, our data proved that NK cell may improve PA-induced lung injury through promoting M1 lung macrophage polarization by secreting exosome. Our results provide a new idea for the treatment of PA lung infection.