Work over the last 40 years has described macrophages as a heterogeneous population that serve as the frontline surveyors of tissue immunity. As a class, macrophages are found in almost every tissue in the body and as distinct populations within discrete microenvironments in any given tissue. During homeostasis, macrophages protect these tissues by clearing invading foreign bodies and/or mounting immune responses. In addition to varying identities regulated by transcriptional programs shaped by their respective environments, macrophage metabolism serves as an additional regulator to temper responses to extracellular stimuli. The area of research known as "immunometabolism" has been established within the last decade, owing to an increase in studies focusing on the crosstalk between altered metabolism and the regulation of cellular immune processes. From this research, macrophages have emerged as a prime focus of immunometabolic studies, although macrophage metabolism and their immune responses have been studied for centuries. During disease, the metabolic profile of the tissue and/or systemic regulators, such as endocrine factors, become increasingly dysregulated. Owing to these changes, macrophage responses can become skewed to promote further pathophysiologic changes. For instance, during diabetes, obesity, and atherosclerosis, macrophages favor a proinflammatory phenotype; whereas in the tumor microenvironment, macrophages elicit an anti-inflammatory response to enhance tumor growth. Herein we have described how macrophages respond to extracellular cues including inflammatory stimuli, nutrient availability, and endocrine factors that occur during and further promote disease progression.

中文翻译：

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体内平衡和疾病期间巨噬细胞对环境刺激的反应。

过去 40 年的工作将巨噬细胞描述为一个异质的群体，充当组织免疫的前线调查员。作为一类，巨噬细胞几乎存在于身体的每个组织中，并且在任何给定组织的离散微环境中作为不同的群体。在稳态期间，巨噬细胞通过清除入侵的异物和/或增加免疫反应来保护这些组织。除了受其各自环境塑造的转录程序调节的不同身份外，巨噬细胞代谢还作为一种额外的调节剂来缓和对细胞外刺激的反应。被称为“免疫代谢”的研究领域是在过去十年中建立起来的，由于越来越多的研究关注新陈代谢改变和细胞免疫过程调节之间的串扰。从这项研究中，巨噬细胞已成为免疫代谢研究的主要焦点，尽管巨噬细胞代谢及其免疫反应已经研究了几个世纪。在疾病期间，组织和/或全身调节因子（如内分泌因子）的代谢谱变得越来越失调。由于这些变化，巨噬细胞反应可能会变得偏斜，以促进进一步的病理生理变化。例如，在糖尿病、肥胖和动脉粥样硬化期间，巨噬细胞倾向于促炎表型。而在肿瘤微环境中，巨噬细胞会引发抗炎反应以促进肿瘤生长。