Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from Pseudomonas aeruginosa

作者：Jing Ge, Min Cao, Yuyao Zhang, Tianqi Wu, Jiayi Liu, Pu Jiang, Hongye He, Zhibin Guo, Shaoqing Ju, Juan Yu · 发表于：Microbiology Spectrum · 年份：2025 · DOI：10.1128/spectrum.01819-24 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、Bacterial Infections and Vaccines、Inflammasome and immune disorders

ABSTRACT The bacterium Pseudomonas aeruginosa is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, it is currently unclear how OMVs from P. aeruginosa (PA-OMVs) affect lung epithelial cells and their impact on oxidative stress, autophagy, and other physiological activities of lung epithelial cells. In this study, we found that PA-OMVs activated oxidative stress and autophagy in cells. We demonstrated that the NLRP3 (NLR family, pyrin domain containing 3) inhibitor MCC950 can enhance autophagy induced by PA-OMVs. The main function of NLRP3 is related to the body’s immune response and inflammation regulation. MCC950 is the most common inhibitor of NLRP3. Additionally, we showed that PA-OMVs not only enhanced the expression of AMP-activated protein kinase, a key regulator of cellular energy homeostasis, and reactive oxygen species, which play a crucial role in cellular signaling and oxidative stress, but also significantly enhanced the expression of NLRP3. Inhibiting the expression of NLRP3 further enhanced the process of PA-OMVs induced autophagy. These results demonstrate that PA-OMVs activate both autophagy and the NLRP3 inflammasome, with NLRP3 suppressing autophagy to a certain extent, hoping to provide broad ideas for the future applications of PA-OMVs. IMPORTANCE The discovery that lung epithelial cells exposed to outer membrane vesicles from Pseudomonas aeruginosa (PA-OMVs) activate...