Airway macrophages (AMs) play key roles in the maintenance of lung immune tolerance. Tissue tailored, highly specialised and strategically positioned, AMs are critical sentinels of lung homoeostasis. In the last decade, there has been a revolution in our understanding of how metabolism underlies key macrophage functions. While these initial observations were made during steady state or using in vitro polarised macrophages, recent studies have indicated that during many chronic lung diseases (CLDs), AMs adapt their metabolic profile to fit their local niche. By generating reactive oxygen species (ROS) for pathogen defence, utilising aerobic glycolysis to rapidly generate cytokines, and employing mitochondrial respiration to fuel inflammatory responses, AMs utilise metabolic reprogramming for host defence, although these changes may also support chronic pathology. This review focuses on how metabolic alterations underlie AM phenotype and function during CLDs. Particular emphasis is given to how our new understanding of AM metabolic plasticity may be exploited to develop AM-focused therapies.

气道巨噬细胞 (AM) 在维持肺部免疫耐受中起着关键作用。组织定制、高度专业化和战略定位，AM 是肺稳态的关键哨兵。在过去十年中，我们对新陈代谢如何构成关键巨噬细胞功能的理解发生了一场革命。虽然这些初步观察是在稳定状态下或使用体外极化巨噬细胞进行的，但最近的研究表明，在许多慢性肺病 (CLD) 期间，AM 会调整其代谢特征以适应其局部生态位。通过产生用于病原体防御的活性氧 (ROS)，利用有氧糖酵解快速产生细胞因子，并利用线粒体呼吸来促进炎症反应，AMs 利用代谢重编程进行宿主防御，尽管这些变化也可能支持慢性病理学。这篇综述的重点是代谢改变如何构成 CLD 期间 AM 表型和功能的基础。特别强调如何利用我们对 AM 代谢可塑性的新理解来开发以 AM 为中心的疗法。