Inflammation, Repair & Development, National Heart & Lung Institute, Imperial College London, London, UK.
Immunol Cell Biol. 2019 Mar;97(3):246-257. doi: 10.1111/imcb.12235. Epub 2019 Feb 15.
The lungs present a challenging immunological dilemma for the host. Anatomically positioned at the environmental interface, they are constantly exposed to antigens, pollutants and microbes, while simultaneously facilitating vital gas exchange. Remarkably, the lungs maintain a functionally healthy state, ignoring harmless inhaled proteins, adapting to toxic environmental insults and limiting immune responses to allergens and pathogenic microbes. This functional strategy of environmental adaptation maintains immune defense, reduces tissue damage, and promotes and sustains lung immune tolerance. At steady state, airway macrophages produce low levels of cytokines, and suppress the induction of innate and adaptive immunity. These cells are primary initiators of lung innate immunity and possess high phagocytic activity to clear particulate antigens and apoptotic cell debris from the airways to regulate the response to infection and inflammation. In response to epithelial injury, resident and recruited macrophages drive tissue repair. In this review, we will focus on the functional importance of macrophages in tissue homeostasis and inflammation in the lung and highlight how environmental cues alter the plasticity and function of lung airway macrophages. We will also discuss mechanisms employed by pulmonary macrophages to promote resolution of tissue inflammation, and how and when this balance is perturbed, they contribute to pathological remodeling in acute and chronic infections and diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.
肺部对宿主来说是一个具有挑战性的免疫学难题。从解剖学位置上看，肺部处于环境界面，不断暴露于抗原、污染物和微生物中，同时还要进行重要的气体交换。值得注意的是，肺部保持着功能健康的状态，忽略了无害的吸入蛋白，适应了有毒的环境刺激，并限制了对过敏原和病原体的免疫反应。这种环境适应的功能策略维持了免疫防御，减少了组织损伤，并促进和维持了肺部的免疫耐受。在稳定状态下，气道巨噬细胞产生低水平的细胞因子，并抑制先天和适应性免疫的诱导。这些细胞是肺部先天免疫的主要启动者，具有高吞噬活性，可清除气道中的颗粒抗原和凋亡细胞碎片，从而调节对感染和炎症的反应。在受到上皮损伤后，驻留和募集的巨噬细胞可促进组织修复。在这篇综述中，我们将重点关注巨噬细胞在肺部组织稳态和炎症中的功能重要性，并强调环境线索如何改变肺气道巨噬细胞的可塑性和功能。我们还将讨论肺巨噬细胞用来促进组织炎症消退的机制，以及这种平衡何时被打破，它们如何导致急性和慢性感染以及哮喘、特发性肺纤维化和慢性阻塞性肺疾病等疾病中的病理性重塑。
