Department of Pediatrics, RWTH Aachen University, 52074 Aachen, Germany.
Int J Mol Sci. 2023 Sep 16;24(18):14173. doi: 10.3390/ijms241814173.
It is well established that the neonatal immune system is different from the adult immune system. A major task of the neonatal immune system is to bridge the achievement of tolerance towards harmless antigens and commensal bacteria while providing protection against pathogens. This is highly important because neonates are immunologically challenged directly after birth by a rigorous change from a semi-allogeneic sterile environment into a world rich with microbes. A so called disease tolerogenic state is typical for neonates and is anticipated to prevent immunopathological damage potentially at the cost of uncontrolled pathogen proliferation. As a consequence, neonates are more susceptible than adults to life-threatening infections. At the basis of a well-functioning immune response, both for adults and neonates, innate immune cells such as monocytes and monocyte-derived macrophages play an essential role. A well-responsive monocyte will alter its cellular metabolism to subsequently induce certain immune effector function, a process which is called immunometabolism. Immunometabolism has received extensive attention in the last decade; however, it has not been broadly studied in neonates. This review focuses on carbohydrate metabolism in monocytes and macrophages in neonates. We will exhibit pathways involving glycolysis, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation and their role in shaping neonates' immune systems to a favorable tolerogenic state. More insight into these pathways will elucidate potential treatments targets in life-threatening conditions including neonatal sepsis or expose potential targets which can be used to induce tolerance in conditions where tolerance is harmfully impaired such as in autoimmune diseases.
众所周知，新生儿的免疫系统与成人的免疫系统不同。新生儿免疫系统的主要任务是在实现对无害抗原和共生菌的耐受的同时，提供对病原体的保护。这一点非常重要，因为新生儿在出生后直接面临免疫挑战，他们从半同种异体无菌环境转变为富含微生物的世界。所谓的疾病耐受状态是新生儿的典型特征，预计可以防止潜在的免疫病理损伤，但其代价是无法控制的病原体增殖。因此，新生儿比成人更容易受到危及生命的感染。在一个功能良好的免疫反应的基础上，无论是成人还是新生儿，先天免疫细胞，如单核细胞和单核细胞衍生的巨噬细胞，都发挥着至关重要的作用。一个反应良好的单核细胞会改变其细胞代谢，随后诱导某些免疫效应功能，这个过程被称为免疫代谢。在过去的十年中，免疫代谢受到了广泛的关注；然而，它在新生儿中并没有得到广泛的研究。这篇综述重点介绍了新生儿单核细胞和巨噬细胞中的糖代谢。我们将展示涉及糖酵解、三羧酸 (TCA) 循环和氧化磷酸化的途径，以及它们在将新生儿的免疫系统塑造为有利的耐受状态中的作用。对这些途径的更深入了解将阐明在危及生命的情况下的潜在治疗靶点，包括新生儿败血症，或暴露在潜在的靶点中，可以在耐受受损的情况下诱导耐受，例如在自身免疫性疾病中。
