Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
Front Immunol. 2024 Jan 8;14:1334205. doi: 10.3389/fimmu.2023.1334205. eCollection 2023.
Neutrophils are the most abundant innate immune cells. Multiple mechanisms allow them to engage a wide range of metabolic pathways for biosynthesis and bioenergetics for mediating biological processes such as development in the bone marrow and antimicrobial activity such as ROS production and NET formation, inflammation and tissue repair. We first discuss recent work on neutrophil development and functions and the metabolic processes to regulate granulopoiesis, neutrophil migration and trafficking as well as effector functions. We then discuss metabolic syndromes with impaired neutrophil functions that are influenced by genetic and environmental factors of nutrient availability and usage. Here, we particularly focus on the role of specific macronutrients, such as glucose, fatty acids, and protein, as well as micronutrients such as vitamin B3, in regulating neutrophil biology and how this regulation impacts host health. A special section of this review primarily discusses that the ways nutrient deficiencies could impact neutrophil biology and increase infection susceptibility. We emphasize biochemical approaches to explore neutrophil metabolism in relation to development and functions. Lastly, we discuss opportunities and challenges to neutrophil-centered therapeutic approaches in immune-driven diseases and highlight unanswered questions to guide future discoveries.
中性粒细胞是最丰富的先天免疫细胞。多种机制允许它们参与广泛的代谢途径，进行生物合成和生物能量代谢，从而介导生物过程，如骨髓中的发育和产生 ROS 和 NET 形成、炎症和组织修复等抗菌活性。我们首先讨论中性粒细胞发育和功能的最新研究进展，以及调节粒细胞生成、中性粒细胞迁移和趋化以及效应功能的代谢过程。然后，我们讨论代谢综合征，其中中性粒细胞功能受损受遗传和环境因素的影响，包括营养物质的可用性和利用。在这里，我们特别关注特定的宏量营养素（如葡萄糖、脂肪酸和蛋白质）以及微量营养素（如维生素 B3）在调节中性粒细胞生物学方面的作用，以及这种调节如何影响宿主健康。这篇综述的一个特别部分主要讨论了营养缺乏如何影响中性粒细胞生物学并增加感染易感性。我们强调了探索与发育和功能相关的中性粒细胞代谢的生化方法。最后，我们讨论了以中性粒细胞为中心的治疗方法在免疫驱动的疾病中的机会和挑战，并强调了未解决的问题，以指导未来的发现。
