Human Lung Mononuclear Phagocytes in Health and Disease.
Human Lung Mononuclear Phagocytes in Health and Disease.
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DOI：
10.3389/fimmu.2017.00499
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发表时间：
2017
影响因子：
7.3
通讯作者：
Smed-Sörensen A
中科院分区：
文献类型：
--
作者：
Baharom F;Rankin G;Blomberg A;Smed-Sörensen A
肺部很容易受到诸如毒素、过敏原和病原体等呼吸道损伤的攻击，因为它们持续暴露在我们呼吸的空气中。我们的免疫系统已经进化到能够在不对肺组织造成附带损害的情况下，提供针对一系列潜在威胁的保护。为了快速检测入侵的病原体，单核细胞、巨噬细胞和树突状细胞(dc) -统称为单核吞噬细胞(MNPs) -在呼吸道中进行检测肺微环境的关键任务，以区分无害和有害抗原，并在必要时启动免疫反应。每种细胞类型都擅长特定的任务：单核细胞产生大量的细胞因子，巨噬细胞具有高度的吞噬能力，而dc擅长激活naïve T细胞。在小鼠模型中进行的大量研究已经建立了稳定状态和感染或炎症期间不同MNPs群体之间的分工。然而，考虑到在难以接近的人体组织中使用稀有细胞的挑战，在小鼠身上的重要发现的翻译才刚刚开始在人类身上进行探索。近年来，关于人肺MNPs的表型和功能的研究取得了重要进展。除了大量的肺泡巨噬细胞外，在稳定状态下的人气道中还发现了三种dc亚群。最近，单核细胞来源的细胞也在健康人肺中被描述。根据样本的来源，如肺组织切除或支气管肺泡灌洗，所恢复的MNPs的特定亚群可能不同。这篇综述提供了在健康和疾病期间调查人类呼吸道MNP种群的现有研究的最新进展。通常，发现炎症性MNPs积聚在肺部疾病患者的肺部。在呼吸道感染或炎症性疾病中，这可能会导致疾病的严重程度，但在癌症患者中，这可能会改善临床结果。通过扩展这方面的知识，可以靶向或调节特定的肺MNPs，以获得有利的反应，从而改善针对呼吸道感染、肺癌或肺部炎症性疾病的预防或治疗策略。
The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)—together termed mononuclear phagocytes (MNPs)—line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary. Each cell type excels at specific tasks: monocytes produce large amounts of cytokines, macrophages are highly phagocytic, whereas DCs excel at activating naïve T cells. Extensive studies in murine models have established a division of labor between the different populations of MNPs at steady state and during infection or inflammation. However, a translation of important findings in mice is only beginning to be explored in humans, given the challenge of working with rare cells in inaccessible human tissues. Important progress has been made in recent years on the phenotype and function of human lung MNPs. In addition to a substantial population of alveolar macrophages, three subsets of DCs have been identified in the human airways at steady state. More recently, monocyte-derived cells have also been described in healthy human lungs. Depending on the source of samples, such as lung tissue resections or bronchoalveolar lavage, the specific subsets of MNPs recovered may differ. This review provides an update on existing studies investigating human respiratory MNP populations during health and disease. Often, inflammatory MNPs are found to accumulate in the lungs of patients with pulmonary conditions. In respiratory infections or inflammatory diseases, this may contribute to disease severity, but in cancer patients this may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs may be targeted or modulated in order to attain favorable responses that can improve preventive or treatment strategies against respiratory infections, lung cancer, or lung inflammatory diseases.