Bi Hongxia, Qin Jiayuan, Huang Jiaqi, Zhong Cejun, Liu Yanbin
Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China.
APMIS. 2024 Sep;132(9):646-656. doi: 10.1111/apm.13444. Epub 2024 Jun 5.
Pseudomonas aeruginosa infection causes pneumonia and sepsis. Previous research found that X-ray radiation can induce P. aeruginosa to release outer membrane vesicles (OMVs) of relatively consistent sizes. This study found that OMVs derived from X-ray-irradiated P. aeruginosa can significantly inhibit lung leakage, inflammatory cell infiltrating into lung, and the production of pro-inflammatory cytokines, IL-1β and TNFα caused by P. aeruginosa infection under preventive and therapeutic administration conditions. Under the same conditions, OMVs also significantly alleviated pathological characteristics of lung injury, including pulmonary edema, pulmonary hemorrhage, and alveolar wall thickening. OMVs also significantly reduced bacterial burdens in peritoneal cavity, accompanied by a reduction in the number of viable bacteria capable of forming bacterial colonies. Pretreating macrophages and neutrophils with OMVs enhances their bactericidal ability. When bacteria were cocultured with treated cells, the number of viable bacteria capable of forming bacterial colonies was significantly reduced. OMVs themselves have not been shown to cause any lung injury or affect bacterial viability. Therefore, OMVs derived from X-ray-irradiated P. aeruginosa may not only be applied in prevention and treatment of diseases associated with P. aeruginosa infection, but also served as an excellent vaccine development platform.
铜绿假单胞菌感染可导致肺炎和败血症。先前的研究发现,X射线辐射可诱导铜绿假单胞菌释放大小相对一致的外膜囊泡(OMV)。本研究发现,在预防性和治疗性给药条件下,源自X射线照射的铜绿假单胞菌的OMV可显著抑制肺渗漏、炎性细胞浸润到肺中以及由铜绿假单胞菌感染引起的促炎细胞因子IL-1β和TNFα的产生。在相同条件下,OMV还显著减轻了肺损伤的病理特征,包括肺水肿、肺出血和肺泡壁增厚。OMV还显著降低了腹腔内的细菌负荷,同时能够形成菌落的活菌数量减少。用OMV预处理巨噬细胞和中性粒细胞可增强其杀菌能力。当细菌与处理过的细胞共培养时,能够形成菌落的活菌数量显著减少。尚未表明OMV本身会导致任何肺损伤或影响细菌活力。因此,源自X射线照射的铜绿假单胞菌的OMV不仅可应用于预防和治疗与铜绿假单胞菌感染相关的疾病,还可作为一个出色的疫苗开发平台。