Jiang Qingkui, Kumar Ranjeet, Zhao Yi, Subbian Selvakumar, Shi Lanbo
Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, Newark, NJ 79103 USA.
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong 523713 China.
One Health Adv. 2025;3(1):5. doi: 10.1186/s44280-025-00070-6. Epub 2025 Mar 21.
Tuberculosis (TB), caused by (), remains a global health challenge. Arginine metabolism is central to immune responses, regulating nitric oxide (NO) production via inducible NO synthase (Nos2) and competing pathways mediated by arginases (Arg1 and Arg2). This study examines the impact of arginine supplementation and arginase inhibition during the acute phase of infection in mouse lungs, focusing on immune function, lung pathology, and mitochondrial function. Arginine supplementation enhanced Nos2 expression, promoted mitophagy, and supported angiogenesis and/or tissue repair by upregulating . These mechanisms synergized to balance pro-inflammatory responses with tissue repair, improving immune defense while mitigating lung damage. In contrast, arginase inhibition disrupted -mediated immune homeostasis, and impaired mitophagy, leading to exacerbated lung pathology. These findings underscore the complementary roles of Nos2 and arginase-mediated pathways in maintaining immune equilibrium during infection. Our results highlight arginine supplementation as a promising host-directed therapy for TB, capable of enhancing protective immunity and facilitating tissue repair. Conversely, caution is warranted for strategies targeting arginase due to potential adverse effects on inflammation resolution and mitochondrial quality control. Future studies should explore the long-term efficacy of arginine-based therapies and their integration with existing antibiotic regimens for optimal TB management.
The online version contains supplementary material available at 10.1186/s44280-025-00070-6.
由（）引起的结核病（TB）仍然是一项全球卫生挑战。精氨酸代谢是免疫反应的核心，通过诱导型一氧化氮合酶（Nos2）调节一氧化氮（NO）的产生，并由精氨酸酶（Arg1和Arg2）介导竞争途径。本研究探讨了在小鼠肺部感染急性期补充精氨酸和抑制精氨酸酶的影响，重点关注免疫功能、肺部病理和线粒体功能。补充精氨酸可增强Nos2表达，促进线粒体自噬，并通过上调（）来支持血管生成和/或组织修复。这些机制协同作用，以平衡促炎反应与组织修复，改善免疫防御同时减轻肺部损伤。相比之下，抑制精氨酸酶会破坏（）介导的免疫稳态，并损害线粒体自噬，导致肺部病理加剧。这些发现强调了Nos2和精氨酸酶介导的途径在感染期间维持免疫平衡中的互补作用。我们的结果突出了补充精氨酸作为一种有前景的结核病宿主导向疗法，能够增强保护性免疫并促进组织修复。相反，由于对炎症消退和线粒体质量控制可能产生的不利影响，针对精氨酸酶的策略应谨慎使用。未来的研究应探索基于精氨酸的疗法的长期疗效，以及它们与现有抗生素方案的整合，以实现最佳的结核病管理。
在线版本包含可在10.1186/s44280-025-00070-6获取的补充材料。
