Lung innate immunity is the first line of defence against inhaled allergens, pathogens and environmental pollutants. Cellular metabolism plays a key role in innate immunity. Catabolic pathways, including glycolysis and fatty acid oxidation (FAO), are interconnected with biosynthetic and redox pathways. Innate immune cell activation and differentiation trigger extensive metabolic changes that are required to support their function. Pro-inflammatory polarisation of macrophages and activation of dendritic cells, mast cells and neutrophils are associated with increased glycolysis and a shift towards the pentose phosphate pathway and fatty acid synthesis. These changes provide the macromolecules required for proliferation and inflammatory mediator production and reactive oxygen species for anti-microbial effects. Conversely, anti-inflammatory macrophages use primarily FAO and oxidative phosphorylation to ensure efficient energy production and redox balance required for prolonged survival. Deregulation of metabolic reprogramming in lung diseases, such as asthma and chronic obstructive pulmonary disease, may contribute to impaired innate immune cell function. Understanding how innate immune cell metabolism is altered in lung disease may lead to identification of new therapeutic targets. This is important as drugs targeting a number of metabolic pathways are already in clinical development for the treatment of other diseases such as cancer.

中文翻译：

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代谢重编程在肺先天免疫中的作用及其对肺部疾病的影响。

肺先天免疫力是抵抗吸入性过敏原，病原体和环境污染物的第一道防线。细胞代谢在先天免疫中起关键作用。分解代谢途径，包括糖酵解和脂肪酸氧化（FAO），与生物合成途径和氧化还原途径相互关联。先天免疫细胞的活化和分化触发了支持其功能所需的大量代谢变化。巨噬细胞的促炎性极化和树突状细胞，肥大细胞和中性粒细胞的活化与糖酵解增加，向戊糖磷酸途径和脂肪酸合成的转变有关。这些变化提供了增殖和炎性介质产生所需的大分子以及抗微生物作用的活性氧。反过来，抗炎巨噬细胞主要使用FAO和氧化磷酸化来确保有效的能量产生和延长生存所需的氧化还原平衡。肺部疾病（例如哮喘和慢性阻塞性肺部疾病）中新陈代谢的重新调节可能会导致先天免疫细胞功能受损。了解肺疾病中先天免疫细胞代谢的变化方式可能导致鉴定新的治疗靶标。这很重要，因为靶向许多代谢途径的药物已经在临床开发中，用于治疗其他疾病，例如癌症。如哮喘和慢性阻塞性肺疾病，可能会导致先天免疫细胞功能受损。了解肺疾病中先天免疫细胞代谢的变化方式可能导致鉴定新的治疗靶标。这很重要，因为靶向许多代谢途径的药物已经在临床开发中，用于治疗其他疾病，例如癌症。如哮喘和慢性阻塞性肺疾病，可能会导致先天免疫细胞功能受损。了解肺疾病中先天免疫细胞代谢的变化方式可能导致鉴定新的治疗靶标。这很重要，因为靶向许多代谢途径的药物已经在临床开发中，用于治疗其他疾病，例如癌症。