固有免疫记忆和受训免疫的发展概述

Overview of the development of innate immune memory and trained immunity

目的回顾20世纪60年代以来固有免疫记忆的发展历程和研究进展,并对其在药物递送领域必然的指导前景进行了展望。方法查阅国内外相关文献96篇,总结固有免疫记忆的发展历程和现有研究成果,寻找其与药物递送系统(drug delivery system,DDS)的关联以及对DDS的未来指导意义。结果固有免疫记忆的发现打破了固有免疫与获得性免疫之间的分界线,被概括为trained immunity,译为"受训免疫"。受训免疫的主要参与者为自然杀伤细胞、单核-巨噬细胞等固有免疫细胞,外界刺激通过细胞表面模式识别受体激活下游信号通路,使细胞核中发生表观遗传重编程,进而改变细胞的代谢方式、受体及细胞因子表达水平,最终改变(增强或减弱)对二次刺激的应答强度。结论固有免疫记忆的发现和受训免疫的提出打破了原有的思维局限,不仅丰富了免疫学的理论体系,而且必将为DDS的未来发展提供新的理论基础与设计依据。

Objective To review the development history and research progress of innate immune memory since the 1960 s,and to prospect the inevitable guiding effects in the field of drug delivery.Methods By combining a total of 96 domestic and foreign literatures,the development history and existing research results of innate immune memory were summarized to find out its relevance to the drug delivery system(DDS)and future guiding significance for DDS.Results The discovery of innate immune memory broke the obvious dividing line between innate immunity and adaptive immunity,which was summarized as trained immunity.The main participants of trained immunity were innate immune cells such as natural killer(NK)cells and mononuclear-macrophages.When these cells stimulated by the external stimuli,the signaling pathways downstream of related pattern recognition receptors(PRRs)would be activated through the receptor-mediated recognition.The altered signal transductions regulated the epigenetic reprogramming in the nucleus,thereby changing the cellular metabolism,PRRs and cytokine expression levels,and ultimately changing(enhancing or attenuating)the intensity of the response to the secondary stimulus.Conclusion The discovery of innate immune memory and trained immunity breaks the original thinking limitations,not only enriches the theoretical system of immunology,but also provides a new theoretical basis and design consideration for the future development of DDS.