小柯机器人

美国德州农工大学Jason Karpac研究组发现，谷氨酸代谢通过引导能量平衡来塑造果蝇的宿主-病原体易感性。该项研究成果于2021年10月27日在线发表在《细胞—代谢》杂志上。

通过使用果蝇，研究人员发现，种群内宿主-病原体易感性的表型变化是由能量平衡（energetic trade-offs）驱动的，并且由感染介导的谷氨酸代谢变化所促进。此外，宿主-病原体易感性受生活史的制约，生活史可调整肌肉中的免疫代谢感应，从而指导维生素依赖性的宿主能量底物从脂肪组织的重新分配（即肌肉-脂肪组织轴）。生活史条件下，肌肉内NF-κB信号的激活强度存在个体间的差异。有限的肌肉内NF-κB信号活动能够增强感染介导的线粒体生物生成和功能，这刺激了谷氨酸脱氢酶依赖的谷氨酸合成。肌肉来源的谷氨酸作为一种系统代谢物，通过调节维生素B酶辅助因子在脂肪组织中的运输和功能来促进脂质动员。

这种能量底物的重新分配改善了病原体的清除，并提高了宿主的生存能力。最后，调整能量平衡的生活史事件可以塑造感染后宿主-病原体易感性的个体间差异。

据介绍，种群中的单个宿主在对细菌病原体相关疾病的敏感性方面经常表现出个体间的差异。

附：英文原文

Title: Glutamate metabolism directs energetic trade-offs to shape host-pathogen susceptibility in Drosophila

Author: Xiao Zhao, Jason Karpac

Issue&Volume: 2021-10-27

Abstract: Individual hosts within populations often show inter-individual variation in theirsusceptibility to bacterial pathogen-related diseases. Utilizing Drosophila, we highlight that phenotypic variation in host-pathogen susceptibility within populationsis driven by energetic trade-offs, facilitated by infection-mediated changes in glutamatemetabolism. Furthermore, host-pathogen susceptibility is conditioned by life history,which adjusts immunometabolic sensing in muscles to direct vitamin-dependent reallocationof host energy substrates from the adipose tissue (i.e., a muscle-adipose tissue axis).Life history conditions inter-individual variation in the activation strength of intra-muscularNF-κB signaling. Limited intra-muscular NF-κB signaling activity allows for enhancedinfection-mediated mitochondrial biogenesis and function, which stimulates glutamatedehydrogenase-dependent synthesis of glutamate. Muscle-derived glutamate acts as asystemic metabolite to promote lipid mobilization through modulating vitamin B enzymaticcofactor transport and function in the adipose tissue. This energy substrate reallocationimproves pathogen clearance and boosts host survival. Finally, life history eventsthat adjust energetic trade-offs can shape inter-individual variation in host-pathogensusceptibility after infection.

DOI: 10.1016/j.cmet.2021.10.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00481-2

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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