铁是一种微量金属元素，对细胞和寄生虫的生存至关重要。铁在脑型弓形虫病（CT）中的作用尚不清楚。右氧基吡啶（DFP）是一种口服活性铁螯合剂，其络合物与铁的摩尔比为3:1（配体:铁），促进尿铁排出以去除体内的多余铁。本实验的目的是观察弓形虫（T. gondii）急性感染大脑中铁的变化，并使用DFP探究CT中铁蛋白质的机制。我们使用在中国流行的优势菌株TgCtwh3建立了体内脑型弓形虫病模型，并以75 mg/kg/d的剂量给小鼠治疗DFP。同时，我们将HT-22细胞用100 μM的DFP进行处理半小时，然后在体外感染细胞与TgCtwh3。采用实时荧光定量PCR检测TgSAG1的水平以反应弓形虫负担。我们使用电感耦合等离子体质谱法、铁离子分析试剂盒、蛋白质印迹分析、谷胱甘肽和谷胱甘硫醇试剂盒、丙二醛试剂盒和免疫荧光染色检测小鼠海马体和HT-22细胞中与铁死亡相关的指标。采用蛋白质印迹分析检测小鼠海马体和细胞中的炎症因子γ干扰素、α肿瘤坏死因子、β转化生长因子和1精氨酸酶。使用苏木精-伊红染色、电子显微镜和莫里斯水迷宫实验评估小鼠的脑损伤。结果显示，TgCtwh3感染后出现了与铁死亡相关的信号通路的激活和小鼠海马体的病理损伤。使用DFP导致了对铁死亡的抗性和病理变化、炎症反应和小鼠弓形虫负担的减轻，延长了小鼠的生存时间。TgCtwh3感染的HT-22细胞在体外激活了铁死亡通路，并被DFP抑制。在TgCtwh3感染的细胞中，炎症反应和线粒体损伤较严重，但这些效应可以通过DFP减轻。我们的研究阐明了T. gondii干扰宿主铁代谢并激活铁死亡的机制，补充了CT的致病机制，进一步证明了DFP治疗CT的潜在价值。版权：© 2023 Wang等。本文是根据知识共享创作的公开获取文章，在原作者和出处被指明的前提下，允许在任何媒介中不受限制地使用、分发和复制。

Iron is a trace metal element that is essential for the survival of cells and parasites. The role of iron in cerebral toxoplasmosis (CT) is still unclear. Deferiprone (DFP) is the orally active iron chelator that binds iron in a molar ratio of 3:1 (ligand:iron) and promotes urinary iron excretion to remove excess iron from the body. The aims of this experiment were to observe the alterations in iron in brains with Toxoplasma gondii (T. gondii) acute infections and to investigate the mechanism of ferroptosis in CT using DFP. We established a cerebral toxoplasmosis model in vivo using TgCtwh3, the dominant strains of which are prevalent in China, and treated the mice with DFP at a dose of 75 mg/kg/d. Meanwhile, we treated the HT-22 cells with 100 μM DFP for half an hour and then infected cells with TgCtwh3 in vitro. A qRT-PCR assay of TgSAG1 levels showed a response to the T. gondii burden. We used inductively coupled plasma mass spectrometry, an iron ion assay kit, Western blot analysis, glutathione and glutathione disulfide assay kits, a malonaldehyde assay kit, and immunofluorescence to detect the ferroptosis-related indexes in the mouse hippocampus and HT-22 cells. The inflammatory factors interferon-γ, tumor necrosis factor-α, transforming growth factor-β, and arginase 1 in the hippocampus and cells were detected using the Western blot assay. Hematoxylin and eosin staining, electron microscopy, and the Morris water maze experiment were used to evaluate the brain injuries of the mice. The results showed that TgCtwh3 infection is followed by the activation of ferroptosis-related signaling pathways and hippocampal pathological damage in mice. The use of DFP led to ferroptosis resistance and attenuated pathological changes, inflammatory reactions and T. gondii burden of the mice, prolonging their survival time. The HT-22 cells with TgCtwh3 activated the ferroptosis pathway and was inhibit by DFP in vitro. In TgCtwh3-infected cells, inflammatory response and mitochondrial damage were severe, but these effects could be reduced by DFP. Our study elucidates the mechanism by which T. gondii interferes with the host's iron metabolism and activates ferroptosis, complementing the pathogenic mechanism of CT and further demonstrating the potential value of DFP for the treatment of CT.Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.