Department of Internal Medicine and Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Physiol Rev. 2023 Jan 1;103(1):313-346. doi: 10.1152/physrev.00031.2021. Epub 2022 Aug 18.
The mechanisms underlying innate immune memory have been extensively explored in the last decades but are in fact largely unknown. Although the specificity of adaptive immune memory in vertebrates is ensured through the recombination of immunoglobulin family genes and clonal expansion, the basic mechanisms of innate immune cells' nonspecific increased responsiveness rely on epigenetic, transcriptional, and metabolic programs after transient stimulation. Changes in these programs result in enhanced responsiveness to secondary challenges with a wide variety of stimuli. This phenomenon is termed "trained immunity" or "innate immune memory." On one hand, trained immunity improves the response to infections and vaccination, facilitating stronger innate immune responses and enhanced protection against a variety of microbial stimuli. Conversely, trained immunity may contribute to the pathophysiology of cardiovascular, autoinflammatory, and neurodegenerative diseases. In this review, we gather the current body of knowledge in this field and summarize the foundations and mechanisms of trained immunity, the different cell types involved, its consequences for health and disease, and the potential of its modulation as a therapeutic tool.
在过去的几十年中，人们已经广泛探索了先天免疫记忆的机制，但实际上这些机制在很大程度上仍是未知的。尽管脊椎动物适应性免疫记忆的特异性是通过免疫球蛋白家族基因的重组和克隆扩增来保证的，但先天免疫细胞非特异性反应性增强的基本机制依赖于短暂刺激后的表观遗传、转录和代谢程序。这些程序的改变导致对各种刺激的二次挑战的反应增强。这种现象被称为“训练免疫”或“先天免疫记忆”。一方面，训练免疫可改善对感染和疫苗接种的反应，促进更强的先天免疫反应，并增强对各种微生物刺激的保护。相反，训练免疫可能导致心血管、自身炎症和神经退行性疾病的病理生理学变化。在这篇综述中，我们收集了该领域的现有知识，并总结了训练免疫的基础和机制、涉及的不同细胞类型、它对健康和疾病的影响，以及作为治疗工具对其进行调节的潜力。
