Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, USA; New York-Presbyterian Hospital, New York, NY, USA.
Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, USA.
Redox Biol. 2024 Oct;76:103329. doi: 10.1016/j.redox.2024.103329. Epub 2024 Aug 27.
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 Mfn1 controls, there were distinct histological differences in lung tissue collected from Mfn1 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.
肺泡巨噬细胞（AM）是免疫反应的关键效应器，对于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，其功能有助于调节细胞周期、先天免疫、自噬、氧化还原信号、钙稳态和 AM 中的线粒体质量控制。在细胞应激下，线粒体可以进行应激诱导的线粒体过度融合（SIMH）。本研究旨在探讨 Mfn1 在 AM 中对活性氧（ROS）的线粒体控制中的作用，以及 Mfn1 缺乏对肺炎链球菌免疫反应的作用。与 Mfn1 对照组相比，从 Mfn1 小鼠中收集的肺组织存在明显的组织学差异，Mfn1 缺失髓样细胞的小鼠观察到的损伤和炎症较少。Mfn1 缺陷型 AM 中的脂质过氧化和 ROS 产生显著减少，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，髓样细胞中 Mfn1 的缺乏减少了肺炎链球菌感染期间的炎症和肺组织损伤。
