State Key Laboratory of Cellular Stress Biology, School of Life Science, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, 361102, China.
Commun Biol. 2024 Jul 5;7(1):817. doi: 10.1038/s42003-024-06479-w.
Macrophages play a pivotal role in orchestrating the immune response against pathogens. While the intricate interplay between macrophage activation and metabolism remains a subject of intense investigation, the role of glutamate oxaloacetate transaminase 1 (Got1) in this context has not been extensively assessed. Here, we investigate the impact of Got1 on macrophage polarization and function, shedding light on its role in reactive oxygen species (ROS) production, pathogen defense, and immune paralysis. Using genetically modified mouse models, including both myeloid specific knockout and overexpression, we comprehensively demonstrate that Got1 depletion leads to reduced ROS production in macrophages. Intriguingly, this impairment in ROS generation does not affect the resistance of Got1 KO mice to pathogenic challenges. Furthermore, Got1 is dispensable for M2 macrophage differentiation and does not influence the onset of LPS-induced immune paralysis. Our findings underscore the intricate facets of macrophage responses, suggesting that Got1 is dispensable in discrete immunological processes.
巨噬细胞在调控针对病原体的免疫反应中发挥着关键作用。虽然巨噬细胞激活和代谢之间的复杂相互作用仍然是一个深入研究的课题,但谷氨酸草酰乙酸转氨酶 1(Got1)在这方面的作用尚未得到广泛评估。在这里,我们研究了 Got1 对巨噬细胞极化和功能的影响,揭示了其在活性氧(ROS)产生、病原体防御和免疫麻痹中的作用。使用基因修饰的小鼠模型,包括髓样细胞特异性敲除和过表达,我们全面证实 Got1 耗竭导致巨噬细胞中 ROS 产生减少。有趣的是,这种 ROS 生成的损伤并不影响 Got1 KO 小鼠对病原体挑战的抵抗力。此外,Got1 对于 M2 巨噬细胞分化是可有可无的,并且不影响 LPS 诱导的免疫麻痹的发生。我们的研究结果强调了巨噬细胞反应的复杂方面,表明在特定的免疫过程中,Got1 是可有可无的。