Von Willebrand Factor Facilitates Intravascular Dissemination of Microsporidia Encephalitozoon hellem.
Von Willebrand Factor Facilitates Intravascular Dissemination of Microsporidia Encephalitozoon hellem.
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冯·维勒布兰德因子促进微孢子虫脑炎孢子虫的血管内传播
DOI：
10.3389/fcimb.2021.694957
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发表时间：
2021
影响因子：
5.7
通讯作者：
Zhou Z
中科院分区：
文献类型：
--
作者：
Bao J;Mo B;An G;Luo J;Poncz M;Pan G;Li T;Zhou Z
微孢子虫是一组孢子形成，真菌相关的病原体，可以感染无脊椎动物和脊椎动物，包括人类。原发感染部位通常是消化道，但也会发生全身感染，并导致肺、脑和肝等器官的损害。微孢子虫的全身传播可能是血管内的，需要在剪切应力的存在下附着和定殖。血管性血友病因子（VWF）是一种大的多聚体血管内蛋白，是血小板和凝血因子的关键附着位点。在本研究中，我们研究了VWF和微孢子虫Encephalitozoon hellem（E。hellem），以及对E. vWF结合后的hellem。微流控检测表明，E. hellem在剪应力下与超大VWF弦结合。离体萌发试验和侵染试验证明，E. hellem能显著提高种子萌发率和侵染率，而VWF阻断抗体可逆转这种作用。质谱分析进一步揭示了VWF孵育改变了E. Hellem包括代谢活性、结构分子水平和蛋白质成熟。我们的研究结果表明，VWF可以结合微孢子虫在循环，并调节其致病性，包括促进萌发和感染率。VWF促进微孢子虫的血管内传播和全身感染。
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 Encephalitozoon hellem (E. hellem), and the modulating effects on E. hellem after VWF binding. Microfluidic assays showed that E. hellem binds to ultra-large VWF strings under shear stress. In vitro germination assay and infection assay proved that E. hellem 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 E. hellem 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.
影响因子：
6.4
作者：
Volontè F;Piubelli L;Pollegioni L
通讯作者：
Pollegioni L