Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, United States.
Semin Cell Dev Biol. 2023 Mar 30;138:128-141. doi: 10.1016/j.semcdb.2022.04.002. Epub 2022 Apr 16.
Infection with pathogenic microbes is a severe threat that hosts manage by activating the innate immune response. In Drosophila melanogaster, the Toll and Imd signaling pathways are activated by pathogen-associated molecular patterns to initiate cellular and humoral immune processes that neutralize and kill invaders. The Toll and Imd signaling pathways operate in organs such as fat body and gut that control host nutrient metabolism, and infections or genetic activation of Toll and Imd signaling also induce wide-ranging changes in host lipid, carbohydrate and protein metabolism. Metabolic regulation by immune signaling can confer resistance to or tolerance of infection, but it can also lead to pathology and susceptibility to infection. These immunometabolic phenotypes are described in this review, as are changes in endocrine signaling and gene regulation that mediate survival during infection. Future work in the field is anticipated to determine key variables such as sex, dietary nutrients, life stage, and pathogen characteristics that modify immunometabolic phenotypes and, importantly, to uncover the mechanisms used by the immune system to regulate metabolism.
感染病原微生物是一种严重的威胁，宿主通过激活先天免疫反应来应对。在黑腹果蝇中，Toll 和 Imd 信号通路被病原体相关分子模式激活，启动细胞和体液免疫过程，中和并杀死入侵物。Toll 和 Imd 信号通路在控制宿主营养代谢的器官（如脂肪体和肠道）中发挥作用，Toll 和 Imd 信号的感染或遗传激活也会诱导宿主脂质、碳水化合物和蛋白质代谢的广泛变化。免疫信号的代谢调节可以赋予宿主对感染的抗性或耐受性，但也可能导致病理学和易感性感染。本文综述了这些免疫代谢表型，以及介导感染期间生存的内分泌信号和基因调控的变化。预计该领域的未来工作将确定关键变量，如性别、膳食营养素、生命阶段和病原体特征，这些变量可以改变免疫代谢表型，重要的是，揭示免疫系统用于调节代谢的机制。
