小柯机器人

德国海德堡DKFZ微生物组与癌症研究中心Eran Elinav和以色列魏茨曼科学研究所Suhaib K. Abdeen共同合作，近期取得重要工作进展。他们研究发现，肺树突细胞代谢是糖尿病患者易受病毒感染的基础。相关研究成果2023年12月13日在线发表于《自然》杂志上。

据介绍，糖尿病患者易患呼吸道病毒感染，包括流感和严重急性呼吸系统综合征冠状病毒2型，其机制尚不清楚。

在急性肺部病毒感染诱导的获得性和遗传性糖尿病小鼠模型中，研究人员证明高血糖会导致共刺激分子表达、抗原转运和T 不同肺树突状细胞（DC）亚群中的细胞启动，驱动有缺陷的抗病毒适应性免疫反应，延迟病毒清除和提高死亡率。从机制上讲，高血糖诱导代谢DC回路的改变，其特征是葡萄糖-乙酰辅酶A分流增加和下游组蛋白乙酰化，导致整体染色质改变。这些反过来又导致关键DC效应物（包括中心抗原呈递相关基因）的表达受损。无论是降糖治疗还是组蛋白乙酰化的药理学调节都能挽救DC功能和抗病毒免疫。

总之，这一研究强调了一个高血糖驱动的代谢-免疫轴在肺部病毒感染期间协调DC功能障碍，并确定了可能在治疗上被利用来减轻感染糖尿病患者加重疾病的代谢检查点。

附：英文原文

Title: Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes

Author: Nobs, Samuel Philip, Kolodziejczyk, Aleksandra A., Adler, Lital, Horesh, Nir, Botscharnikow, Christine, Herzog, Ella, Mohapatra, Gayatree, Hejndorf, Sophia, Hodgetts, Ryan-James, Spivak, Igor, Schorr, Lena, Fluhr, Leviel, Kviatcovsky, Denise, Zacharia, Anish, Njuki, Suzanne, Barasch, Dinorah, Stettner, Noa, Dori-Bachash, Mally, Harmelin, Alon, Brandis, Alexander, Mehlman, Tevie, Erez, Ayelet, He, Yiming, Ferrini, Sara, Puschhof, Jens, Shapiro, Hagit, Kopf, Manfred, Moussaieff, Arieh, Abdeen, Suhaib K., Elinav, Eran

Issue&Volume: 2023-12-13

Abstract: People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and Tcell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

DOI: 10.1038/s41586-023-06803-0

Source: https://www.nature.com/articles/s41586-023-06803-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html