Molecular and Cellular Mechanisms Modulating Trained Immunity by Various Cell Types in Response to Pathogen Encounter.
Molecular and Cellular Mechanisms Modulating Trained Immunity by Various Cell Types in Response to Pathogen Encounter.
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DOI：
10.3389/fimmu.2021.745332
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kalergis AM
中科院分区：
文献类型：
--
作者：
Acevedo OA;Berrios RV;Rodríguez-Guilarte L;Lillo-Dapremont B;Kalergis AM
训练免疫的诱导代表了一个新兴的概念，即先天免疫细胞获得记忆表型的能力，这是适应性反应的典型标志。训练免疫建立过程中调节的关键点包括不同的天然免疫细胞和非免疫细胞的表观遗传、代谢和功能变化。关于表观遗传变化，已描述了长非编码RNA(LncRNAs)作为分子支架，允许组装催化染色质表观遗传变化的染色质重塑复合体。另一方面，在这个过程中发生的相关代谢变化包括糖酵解速率增加和三羧酸(TCA)循环中代谢产物的积累，从而调节组蛋白修饰酶的活性，最终驱动表观遗传变化。已建立的训练性免疫的功能后果包括增强细胞因子的产生、增加抗原呈递和增强抗菌反应。在这篇文章中，我们将讨论目前关于不同细胞亚群获得训练免疫表型的能力的知识，以及触发这种反应的分子机制。这一认识将有助于基于调控训练免疫发展的表观遗传和代谢线索的调控而开发针对传染病的广谱治疗。
The induction of trained immunity represents an emerging concept defined as the ability of innate immune cells to acquire a memory phenotype, which is a typical hallmark of the adaptive response. Key points modulated during the establishment of trained immunity include epigenetic, metabolic and functional changes in different innate-immune and non-immune cells. Regarding to epigenetic changes, it has been described that long non-coding RNAs (LncRNAs) act as molecular scaffolds to allow the assembly of chromatin-remodeling complexes that catalyze epigenetic changes on chromatin. On the other hand, relevant metabolic changes that occur during this process include increased glycolytic rate and the accumulation of metabolites from the tricarboxylic acid (TCA) cycle, which subsequently regulate the activity of histone-modifying enzymes that ultimately drive epigenetic changes. Functional consequences of established trained immunity include enhanced cytokine production, increased antigen presentation and augmented antimicrobial responses. In this article, we will discuss the current knowledge regarding the ability of different cell subsets to acquire a trained immune phenotype and the molecular mechanisms involved in triggering such a response. This knowledge will be helpful for the development of broad-spectrum therapies against infectious diseases based on the modulation of epigenetic and metabolic cues regulating the development of trained immunity.