Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Republic of Korea; College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Biochem Pharmacol. 2018 Aug;154:424-434. doi: 10.1016/j.bcp.2018.06.009. Epub 2018 Jun 8.
Despite remarkable advances in medical science, infection-associated diseases remain among the leading causes of death worldwide. There is a great deal of interest and concern at the rate at which new pathogens are emerging and causing significant human health problems. Expanding our understanding of how cells regulate signaling networks to defend against invaders and retain cell homeostasis will reveal promising strategies against infection. It has taken scientists decades to appreciate that eukaryotic aminoacyl-tRNA synthetases (ARSs) play a role as global cell signaling mediators to regulate cell homeostasis, beyond their intrinsic function as protein synthesis enzymes. Recent discoveries revealed that ubiquitously expressed standby cytoplasmic ARSs sense and respond to danger signals and regulate immunity against infections, indicating their potential as therapeutic targets for infectious diseases. In this review, we discuss ARS-mediated anti-infectious signaling and the emerging role of ARSs in antimicrobial immunity. In contrast to their ability to defend against infection, host ARSs are inevitably co-opted by viruses for survival and propagation. We therefore provide a brief overview of the communication between viruses and the ARS system. Finally, we discuss encouraging new approaches to develop ARSs as therapeutics for infectious diseases.
尽管医学科学取得了显著进步，但感染相关疾病仍是全球主要死亡原因之一。新病原体的出现速度及其导致的重大人类健康问题引起了广泛关注和担忧。深入了解细胞如何调节信号网络以抵御入侵并维持细胞内稳态，将揭示出对抗感染的有前景的策略。科学家们花了几十年的时间才意识到，真核生物的氨酰-tRNA 合成酶 (ARS) 除了作为蛋白质合成酶的固有功能外，还作为全球细胞信号转导介质发挥作用，调节细胞内稳态。最近的发现表明，普遍表达的备用细胞质 ARS 能够感知和响应危险信号，并调节抗感染免疫，这表明它们有作为治疗感染性疾病的潜在靶点。在这篇综述中，我们讨论了 ARS 介导的抗感染信号转导以及 ARS 在抗菌免疫中的新兴作用。与它们抵御感染的能力形成对比的是，宿主 ARS 不可避免地被病毒用于生存和繁殖。因此，我们简要概述了病毒与 ARS 系统之间的通讯。最后，我们讨论了令人鼓舞的新方法，即将 ARS 开发为治疗感染性疾病的药物。
