伯氏疟原虫介导的NRF2在感染肝细胞中的激活提高了寄生虫的存活

IF 2.6 2区 生物学 Q3 CELL BIOLOGY
Annina Bindschedler, J. Schmuckli-Maurer, Rahel Wacker, Nicolas Kramer, Ruth Rehmann, R. Caldelari, V. Heussler
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引用次数: 2

摘要

疟原虫是疟疾的病原体,最初侵入并在肝细胞中发育,它位于寄生液泡(PV)中。一个被入侵的寄生虫会发展成成千上万的子寄生虫。宿主细胞的存活对于成功完成肝脏阶段的发育至关重要。核因子红系衍生的2-相关因子2(NRF2)是一种已知的转录因子,当被激活时可诱导细胞保护基因的转录。在这里,我们发现NRF2在伯氏疟原虫感染的肝细胞中被激活。我们观察到,这种NRF2的激活依赖于PV膜驻留的p62募集KEAP1,即NRF2的负调节因子。破坏NRF2基因导致寄生虫存活率降低,表明NRF2信号传导是肝细胞中寄生虫发育的重要事件。总之,我们的观察揭示了疟原虫如何在肝脏发育阶段确保宿主细胞存活的新机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasmodium berghei-Mediated NRF2 Activation in Infected Hepatocytes Enhances Parasite Survival
The protozoan parasite Plasmodium, causative agent of malaria, initially invades and develops in hepatocytes where it resides in a parasitophorous vacuole (PV). A single invaded parasite develops into thousands of daughter parasites. Survival of the host cell is crucial for successful completion of liver stage development. Nuclear factor erythroid-derived 2-related factor 2 (NRF2) is a transcription factor known to induce transcription of cytoprotective genes when activated. Here we show that NRF2 is activated in Plasmodium berghei-infected hepatocytes. We observed that this NRF2 activation depends on PV membrane resident p62 recruiting KEAP1, the negative regulator of NRF2. Disrupting the NRF2 gene results in reduced parasite survival, indicating that NRF2 signaling is an important event for parasite development in hepatocytes. Together, our observations uncovered a novel mechanism of how Plasmodium parasites ensure host cell survival during liver stage development.
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来源期刊
Cellular Microbiology
Cellular Microbiology 生物-微生物学
CiteScore
9.70
自引率
0.00%
发文量
26
审稿时长
3 months
期刊介绍: Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.
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