Department of Internal Medicine and Research Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (H.T., N.P.R., L.A.B.J., M.G.N., S.B.).
Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania (L.A.B.J.).
Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):55-61. doi: 10.1161/ATVBAHA.120.314212. Epub 2020 Oct 22.
Adaptive immune responses are characterized by antigen specificity and induction of lifelong immunologic memory. Recently, it has been reported that innate immune cells can also build immune memory characteristics-a process termed trained immunity. Trained immunity describes the persistent hyperresponsive phenotype that innate immune cells can develop after brief stimulation. Pathogenic stimuli such as microorganisms, and also endogenous molecules including uric acid, oxidized LDL (low-density lipoprotein), and catecholamines, are capable of inducing memory in monocytes and macrophages. While trained immunity provides favorable cross-protection in the context of infectious diseases, the heightened immune response can be maladaptive in diseases driven by chronic systemic inflammation, such as atherosclerosis. Trained immunity is maintained by distinct epigenetic and metabolic mechanisms and persists for at least several months in vivo due to reprogramming of myeloid progenitor cells. Additionally, certain nonimmune cells are also found to exhibit trained immunity characteristics. Thus, trained immunity presents an exciting framework to develop new approaches to vaccination and also novel pharmacological targets in the treatment of inflammatory diseases.
适应性免疫反应的特征是抗原特异性和诱导终身免疫记忆。最近，据报道，先天免疫细胞也可以建立免疫记忆特征——这一过程被称为训练有素的免疫。训练有素的免疫描述了先天免疫细胞在短暂刺激后可以发展出的持久超敏表型。病原体刺激物，如微生物，以及包括尿酸、氧化 LDL（低密度脂蛋白）和儿茶酚胺在内的内源性分子，能够在单核细胞和巨噬细胞中诱导记忆。虽然在传染病的情况下，训练有素的免疫提供了有利的交叉保护，但在由慢性系统性炎症驱动的疾病中，增强的免疫反应可能是适应不良的，例如动脉粥样硬化。训练有素的免疫是通过独特的表观遗传和代谢机制维持的，并且由于髓样祖细胞的重新编程，在体内至少持续数月。此外，还发现某些非免疫细胞也表现出训练有素的免疫特征。因此，训练有素的免疫为开发疫苗的新方法以及治疗炎症性疾病的新型药理学靶点提供了一个令人兴奋的框架。
