Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hanover, Germany.
Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hanover, Germany.
Front Immunol. 2020 Apr 30;11:688. doi: 10.3389/fimmu.2020.00688. eCollection 2020.
The restricted capacity of newborn infants to mount inflammatory responses toward microbial challenges has traditionally been linked to the high risk of septic diseases during the neonatal period. In recent years, substantial evidence has been provided that this characteristic of the neonatal immune system is actually a meaningful physiologic state that is based on specific transiently active cellular and molecular mechanisms and required for a favorable course of postnatal immune adaptation. The identification of physiologically high amounts of S100-alarmins in neonates has been one of the crucial pieces in the puzzle that contributed to the change of concept. In this context, innate immune immaturity could be redefined and assigned to the epigenetic silence of adult-like cell-autonomous regulation at the beginning of life. S100-alarmins represent an alternative age-specific mechanism of immune regulation that protects neonates from hyperinflammatory immune responses. Here, we summarize how infants are provided with S100-alarmins and why these allow an uneventful clash between the innate immune system and the extrauterine world. The mode of action of S100-alarmins is highlighted including their tuning functions at multiple levels for establishing a state of homeostasis with the environment in the newborn individual.
新生儿对微生物挑战产生炎症反应的能力有限，这与新生儿期败血症疾病的高风险传统上有关。近年来，大量证据表明，新生儿免疫系统的这一特征实际上是一种有意义的生理状态，它基于特定的短暂活跃的细胞和分子机制，是对产后免疫适应的良好过程所必需的。在这个背景下，先天免疫不成熟可以被重新定义，并被分配给生命开始时成人样细胞自主调节的表观遗传沉默。S100-警报素代表了一种替代的年龄特异性免疫调节机制，可保护新生儿免受过度炎症性免疫反应的影响。在这里，我们总结了婴儿是如何获得 S100-警报素的，以及为什么这些警报素允许先天免疫系统与子宫外世界之间发生无冲突的碰撞。强调了 S100-警报素的作用方式，包括它们在多个水平上的调节功能，以在新生儿个体中建立与环境的体内平衡状态。
