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血管性血友病因子促进微孢子虫的血管内传播。

Von Willebrand Factor Facilitates Intravascular Dissemination of Microsporidia .

机构信息

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, China.

出版信息

Front Cell Infect Microbiol. 2021 May 21;11:694957. doi: 10.3389/fcimb.2021.694957. eCollection 2021.

Abstract

Microsporidia are a group of spore-forming, fungus-related pathogens that can infect both invertebrates and vertebrates including humans. The primary infection site is usually digestive tract, but systemic infections occur as well and cause damages to organs such as lung, brain, and liver. The systemic spread of microsporidia may be intravascular, requiring attachment and colonization in the presence of shear stress. Von Willebrand Factor (VWF) is a large multimeric intravascular protein and the key attachment sites for platelets and coagulation factors. Here in this study, we investigated the interactions between VWF and microsporidia (), and the modulating effects on after VWF binding. Microfluidic assays showed that binds to ultra-large VWF strings under shear stress. germination assay and infection assay proved that significantly increased the rates of germination and infection, and these effects would be reversed by VWF blocking antibody. Mass spectrometry analysis further revealed that VWF-incubation altered various aspects of including metabolic activity, levels of structural molecules, and protein maturation. Our findings demonstrated that VWF can bind microsporidia in circulation, and modulate its pathogenicity, including promoting germination and infection rate. VWF facilitates microsporidia intravascular spreading and systemic infection.

摘要

微孢子虫是一组形成孢子的、与真菌有关的病原体,可感染包括人类在内的无脊椎动物和脊椎动物。主要感染部位通常是消化道,但也会发生全身感染,并导致肺、脑和肝等器官受损。微孢子虫的全身传播可能是血管内的,需要在切变应力存在的情况下附着和定植。血管性血友病因子(VWF)是一种大型的多聚血管内蛋白,是血小板和凝血因子的关键附着部位。在这项研究中,我们研究了 VWF 与微孢子虫之间的相互作用,以及 VWF 结合后对 的调节作用。微流控分析表明, 在切变应力下与超大 VWF 链结合。 发芽试验和感染试验证明, 显著提高了发芽和感染的速度,而 VWF 阻断抗体可以逆转这些作用。质谱分析进一步揭示了 VWF 孵育改变了 的各个方面,包括代谢活性、结构分子水平和蛋白质成熟度。我们的研究结果表明,VWF 可以在循环中与微孢子虫结合,并调节其致病性,包括促进发芽和感染率。VWF 促进微孢子虫的血管内传播和全身感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1082/8176104/60905a088795/fcimb-11-694957-g001.jpg

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