Glutamate oxaloacetate transaminase 1 is dispensable in macrophage differentiation and anti-pathogen response

• Published in: Communications biology Vol. 7; no. 1; pp. 817 - 10
• Main Authors: Zhang, Lishan, Wu, Zhengyi, Qiu, Xuanhui, Zhang, Jia, Cheng, Shih-Chin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 631/250; 631/250/254; 64/60; Animal models; Animals; Aspartate Aminotransferase, Cytoplasmic - genetics; Aspartate Aminotransferase, Cytoplasmic - metabolism; Biomedical and Life Sciences; Cell activation; Cell Differentiation; Immune response; Life Sciences; Lipopolysaccharides - pharmacology; Macrophage Activation - genetics; Macrophages; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Paralysis; Pathogens; Reactive oxygen species; Reactive Oxygen Species - metabolism; Transaminase
• ISSN: 2399-3642; 2399-3642
• 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. A comprehensive evaluation, incorporating knockout and overexpression experiments, reveals that Got1 is dispensable in macrophage differentiation.