摘要
随着铜绿假单胞菌(铜绿)的耐药性逐年增强, 铜绿感染已经成为公共医疗卫生的重点关注问题。线粒体自噬及其介导的线粒体功能障碍在多种细菌感染中已被报道, 但线粒体功能障碍在宿主调控铜绿感染中的作用尚不明确。因此, 本研究建立铜绿刺激小鼠巨噬细胞感染模型和小鼠急性铜绿感染模型, 探讨铜绿是否通过诱导线粒体自噬改变线粒体功能, 进而影响宿主免疫炎症反应和细胞毒性, 并通过监测生存率和肺组织病理学变化进一步确定线粒体自噬在小鼠铜绿体内感染模型中的作用。结果表明, 铜绿引起小鼠腹腔巨噬细胞线粒体功能障碍, 并通过线粒体自噬途径清除铜绿刺激引起的活性氧(ROS)累积, 从而抑制铜绿引起的促炎性细胞因子分泌并增强细胞毒性。体内实验进一步确认线粒体自噬在铜绿体内感染中的作用。
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Acknowledgments
This work was supported by the Basic Science (Natural Science) Research Project of Higher Education of Jiangsu Province (No. 21KJB230001), the Open-End Funds of Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening (No. HY202101), the Lianyungang City Science and Technology Bureau Science and Technology Plan (Social Development) Project (No. SF2140), the 2022 Medical Research guiding Project of Jiangsu Provincial Health Commission (No. Z2022070), the 2023 Jiangsu Graduate Research Innovation Plan Project (No. SJCX23_1838), and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
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Haitao YANG: research design and execution, and writing the first manuscript version. Yan WANG: experimental material collection, research execution, writing review, and editing. Hui FAN, Feixue LIU, and Huimiao FENG: conceptualization, software, formal analysis, and visualization. Xueqing LI, Mingyi CHU, Enzhuang PAN, and Daoyang TENG: investigation and data curation. Huizhen CHEN and Jingquan DONG: methodology, data curation, and project administration. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Haitao YANG, Yan WANG, Hui FAN, Feixue LIU, Huimiao FENG, Xueqing LI, Mingyi CHU, Enzhuang PAN, Daoyang TENG, Huizhen CHEN, and Jingquan DONG declare that there is no conflict of interest among them.
All institutional and national guidelines for the care and use of laboratory animals were followed. The animal procedures were permitted by the Ethics Committee of Jiangsu Ocean University, Lianyungang, China (No. 2022221095).
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Yang, H., Wang, Y., Fan, H. et al. Pseudomonas aeruginosa-induced mitochondrial dysfunction inhibits proinflammatory cytokine secretion and enhances cytotoxicity in mouse macrophages in a reactive oxygen species (ROS)-dependent way. J. Zhejiang Univ. Sci. B 24, 1027–1036 (2023). https://doi.org/10.1631/jzus.B2300051
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DOI: https://doi.org/10.1631/jzus.B2300051