Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy.
Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
Pediatr Res. 2020 Jan;87(2):399-405. doi: 10.1038/s41390-019-0647-6. Epub 2019 Nov 5.
The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or "training" of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.
新生儿在生命的最初几天需要消耗大量能量，因为代谢功能会发生巨大变化，以适应出生后的环境和生理转变。人们越来越认识到，代谢途径不仅对营养至关重要，而且在调节炎症和宿主对感染的反应方面也起着重要作用。由于新生儿的免疫反应具有独特的功能，高度依赖先天免疫机制，因此易受感染。代谢与免疫反应之间的相互作用越来越受到重视，因为代谢途径的变化会驱动先天免疫细胞的功能和激活，从而影响宿主对病原体的反应。此外，代谢物（如乙酰辅酶 A（acetyl-CoA）和琥珀酸）具有免疫调节特性，并且作为涉及先天免疫细胞的表观遗传重编程或初始感染后“训练”的酶的辅助因子。高灵敏度代谢组学方法可让我们定义代谢特征在个体发育过程中的变化，以及免疫接种或感染对其的干扰，从而将代谢途径与免疫细胞效应功能联系起来。描述免疫代谢的个体发育将为预防、诊断和治疗新生儿败血症提供新的机会。
