Alveolar macrophages (AM) are key effectors of the immune response and are essential for host responses to S. pneumoniae. Mitochondria are highly dynamic organelles whose function aids in regulating the cell cycle, innate immunity, autophagy, redox signaling, calcium homeostasis, and mitochondrial quality control in AM. In response to cellular stress, mitochondria can engage in stress-induced mitochondrial hyperfusion (SIMH). The current study aimed to investigate the role of Mfn1 on mitochondrial control of reactive oxygen species (ROS) in AMs and the role of Mfn1 deficiency on immune responses to S. pneumoniae. Compared to Mfn1FloxCre− controls, there were distinct histological differences in lung tissue collected from Mfn1Floxed; CreLysM mice, with less injury and inflammation observed in mice with Mfn1 deficient myeloid cells. There was a significant decrease in lipid peroxidation and ROS production in Mfn1 deficient AM that was associated with increased superoxide dismutase (SOD) and antioxidant activity. Our findings demonstrate that Mfn1 deficiency in myeloid cells decreased inflammation and lung tissue injury during S. pneumoniae infection.

中文翻译：

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Mitofusin 1 在肺炎链球菌期间介导肺泡巨噬细胞活性氧中的作用


肺泡巨噬细胞 （AM） 是免疫反应的关键效应物，对宿主对肺炎链球菌的反应至关重要。线粒体是高度动态的细胞器，其功能有助于调节 AM 中的细胞周期、先天免疫、自噬、氧化还原信号传导、钙稳态和线粒体质量控制。为了响应细胞应激，线粒体可以参与应激诱导的线粒体过度融合 （SIMH）。目前的研究旨在探讨 Mfn1 对 AM 中活性氧 （ROS） 线粒体控制的作用以及 Mfn1 缺陷对肺炎链球菌免疫反应的作用。与 Mfn1FloxCre− 对照相比，从 Mfn1Floxed 收集的肺组织存在明显的组织学差异;CreLysM 小鼠，在 Mfn1 缺陷髓细胞小鼠中观察到的损伤和炎症较少。Mfn1 缺陷型 AM 中脂质过氧化和 ROS 产生显着减少，这与超氧化物歧化酶 （SOD） 和抗氧化活性增加有关。我们的研究结果表明，髓系细胞中的 Mfn1 缺乏减少了肺炎链球菌感染期间的炎症和肺组织损伤。