单核/巨噬细胞发生受训后免疫的机制研究进展

Research advance on mechanism of trained immunity in monocytes/macrophages

只有适应性免疫系统才具有记忆性的传统观点目前正逐渐受到挑战。在缺乏适应性免疫的生物体(植物、无脊椎动物)以及脊椎动物体内,均发现了固有免疫系统(自然杀伤细胞、单核/巨噬细胞等)在再次接触相同或无关病原体刺激时表现出增强或减弱的免疫反应,这一现象被称为受训后免疫(TI)或固有免疫记忆。经典的适应性免疫记忆具有特异性、抗原依赖性、由基因重排介导等特点,而TI则被认为是非特异性的、抗原无关的、由表观遗传学及代谢重编程介导的,因此TI是机体免疫记忆的一种新补充。研究证实TI是一把双刃剑,在维持健康和促进疾病中发挥重要作用;阐明TI的调控机制,将为感染性疾病、免疫缺陷病及炎症疾病等疾病的发病机理研究以及新型疫苗的研发提供新颖视角。本文对TI的发现、特点、发生机制等方面进行综述,重点阐述表观遗传学及代谢重编程在单核巨噬细胞发生TI中的作用及最新的机制研究进展。

The traditional view that only the adaptive immune system has memory is gradually being challenged.In organisms lacking adaptive immunity(such as plants and invertebrates)as well as in vertebrates,the innate immune system(natural killer cells,monocytes/macrophages,etc) can exhibit an enhanced or reduced immune response after a second encounter with the same or unrelated pathogens or stimuli.This phenomenon is now termed by "trained immunity" or "innate immune memory".Classical adaptive immune memory is considered to be specific,antigen-dependent and mediated by gene rearrangement,while TI is considered to be nonspecific,antigen-independent and to be mediated by epigenetics and metabolic reprogramming.Therefore,TI is a new supplement to immune memory.Accumulating evidence has shown that TI is a double-edged sword,which plays an important role both in the maintenance of human health and the occurrence and development of diseases.Clarifying the regulatory mechanism of how TI occurs will provide a novel perspective for the prevention and treatment of infections diseases,immunodeficiency diseases and inflammatory diseases,as well as the design and development of new vaccines.This article is meant to review the discovery,characteristics and mechanism of TI phenomenon,with a special focus on the role and mechanism of epigenetic and metabolic reprogramming in TI induction.