NK cell-derived exosomes improved lung injury in mouse model of Pseudomonas aeruginosa lung infection
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The Journal of Physiological Sciences Open Access
ORIGINAL PAPER
NK cell‑derived exosomes improved lung injury in mouse model of Pseudomonas aeruginosa lung infection Ruiqi Jia1, Kuili Cui2, Zhenkui Li2, Yuan Gao2, Bianfang Zhang2, Zhixia Wang3 and Junwei Cui2*
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 PAinfected 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. Keywords: Pseudomonas aeruginosa, Lung infection, Natural killer cell, Macrophage, Exosome Background Pseudomonas aeruginosa (PA) is a Gram-negative bacterium within the hospital environment, and the major cause of nosocomial pneumonia which mainly occurs in the patients with chronic obstructive pulmonary disease and cystic fibrosis, and the immunocompromised [1, 2]. Currently, due to the limitation of antibiotic therapy caused by the increasing multidrug resistance microbe, PA was listed in the most critical group of drug-resistant germs by the World Health Organization [3, 4]. The *Correspondence: [email protected] 2 Tuberculosis Medicine, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Jiankang Road, Xinxiang 453003, China Full list of author information is available at the end of the article
molecular mechanisms of governing immune response to PA lung infection remains not fully unclear. For pulmonary bacterial infection, PA must overcome the innate host defense responses. During the development of PA infection, immune cells, such as dendritic cells, neutrophils, macrophages and natural killer (NK) cells, were recruited to the site of infection to clear PA, while excessive inflammation enhances bacterial infection and PA-induced lung injury [5]. Macrophage is a
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