Tummolo Albina, Melpignano Livio
Department of Metabolic Diseases, Clinical Genetics and Diabetology, Giovanni XXIII Children Hospital, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy.
Medical Direction, Giovanni XXIII Children Hospital, Azienda Ospedaliero-Universitaria Consorziale, 70126 Bari, Italy.
Microorganisms. 2023 Oct 12;11(10):2545. doi: 10.3390/microorganisms11102545.
Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). The basic molecular mechanisms behind the role of infections in these conditions have not been completely clarified. This review points out the different mechanisms behind the relationship between IMDs and infections, providing an overview of this still-under-investigated area. Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. In addition, a dietary regimen with a reduced intake of both micro- and macronutrients can potentially compromise the ability of the immune system to deal with an infection. There is recent pre-clinical evidence showing that during infections there may be a disruption of substrates of various metabolic pathways, leading to further cellular metabolic alteration. Therefore, infective agents may affect cellular metabolic pathways, by mediation or not of an altered immune system. The data reviewed here strongly suggest that the role of infections in many types of IMDs deserves greater attention for a better management of these disorders and a more focused therapeutic approach.
感染是急性代谢紊乱的主要原因和/或许多遗传性代谢疾病（IMD）临床病程恶化的原因。感染在这些情况下所起作用背后的基本分子机制尚未完全阐明。本综述指出了IMD与感染之间关系背后的不同机制，对这一仍未得到充分研究的领域进行了概述。传统上，感染被认为是由于能量产生的生化缺陷导致免疫系统受损的结果。一种辅助性致病机制与由于先天性糖基化缺陷导致的蛋白质连接聚糖组成的基因改变有关。此外，微量营养素和常量营养素摄入量减少的饮食方案可能会潜在地损害免疫系统应对感染的能力。最近有临床前证据表明，在感染期间，各种代谢途径的底物可能会受到干扰，从而导致进一步的细胞代谢改变。因此，感染因子可能通过或不通过改变的免疫系统介导来影响细胞代谢途径。这里回顾的数据强烈表明，感染在许多类型的IMD中的作用值得更多关注，以便更好地管理这些疾病并采取更有针对性的治疗方法。
