谷氨酸的利用促进了树突细胞中线粒体ROS的快速产生,并推动了血症期间的全身炎症
Ivo Fabrik1, Petra Spidlova2, Lukas Prchal1
1Biomedical Research Center, University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czechia.
Science advances
|August 29, 2025
概括
通过重编程线粒体新陈代谢来劫持树突细胞. 这种新陈代谢导致炎症和细菌扩散, 使宿主代谢成为治疗点.
科学领域:
- 免疫学
- 微生物学
- 细胞代谢
背景情况:
- 细胞内细菌可以颠覆树突细胞 (DC),促进病原体的传播和免疫病理.
- 细菌操纵DC的确切机制在很大程度上仍未被定义.
研究的目的:
- 阐明Francisella tularensis利用宿主树突细胞的机制.
- 研究 mitochondrial 代谢在 DC 颠覆中的作用.
主要方法:
- 感染DC的线粒体关联和代谢分析.
- 研究三碳酸循环中的蛋白质乙化和基质利用.
- 对线粒体反应性氧物种 (mtROS) 生产和下游信号通路的评估.
- 在体内研究评估阻断谷氨酸利用对细菌传播和炎症的影响.
主要成果:
- 在内部化后,Francisella tularensis迅速与DC线粒体结合.
- 细菌感染诱导线粒体的新陈代谢,使用谷氨酸作为主要的三酸循环基质.
- 这种代谢转变导致线粒体反应性氧物种 (mtROS) 的产生增加,激活p38依赖的促炎基因表达.
- 通过DC抑制谷氨酸利用,在体内消除了细菌的传播和减少了炎症.
结论:
- 通过劫持线粒体新陈代谢来破坏树突细胞.
- 谷氨酸为燃料的mtROS产生是细菌诱导的DC激活和炎症的关键机制.
- 针对宿主代谢途径,特别是谷氨酸的利用,是对抗血症的潜在治疗策略.
相关概念视频
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Liver Regeneration
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Hormones Regulating Blood Glucose
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
Vascular Spasm
The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...
Acute Inflammation I: Cellular Phase
The cellular phase of acute inflammation is a tightly orchestrated sequence of events that recruits leukocytes, primarily neutrophils, to sites of tissue injury or infection. Following the initial vascular changes, this phase ensures effective immune cell migration, activation, and function at the affected site to eliminate pathogens and initiate tissue repair.Leukocyte Recruitment CascadeLeukocyte recruitment happens in four steps: margination, adhesion, transmigration, and chemotaxis. Reduced...
Hyperglycemia
Hyperglycemia is an abnormally high blood glucose level. It is diagnosed by fasting glucose ≥126 mg/dL, 2-hour oral glucose tolerance test (or OGTT) ≥200 mg/dL, random glucose ≥200 mg/dL with symptoms, or HbA1c ≥6.5%. However, HbA1c results may be unreliable in certain conditions, such as anemia or hemoglobinopathies, and the diagnosis should be confirmed unless classic symptoms are present. Postprandial hyperglycemia is typically considered significant when glucose levels exceed 180 mg/dL two...


