Von Willebrand Factor Facilitates Intravascular Dissemination of Microsporidia Encephalitozoon hellem.

Jialing Bao,Guoqing Pan,Guozhen An,Zeyang Zhou,Tian Li,Mortimer Poncz,Biying Mo,Jian Luo

doi:10.3389/fcimb.2021.694957

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 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.

Highlights

Microsporidia are a group of intracellular parasites that have recently been re-classified to fungi (Hirt et al, 1999; Han and Weiss, 2017)
To investigate whether Von Willebrand Factor (VWF) is essential for hematogenous dissemination of microsporidia, FL-VWF was perfused with E. hellem spores through the microfluidic chamber under shear stress
Glucose-6-phosphate isomerase, an enzyme involved in glucose metabolism (Kugler and Lakomek, 2000); YOP1, a protein associated with vesicle-mediated transportation and invasion (Viljanen et al, 1991); and aminopeptidase, an enzyme associated with parasitophorous vacuole formation (Lu et al, 2020), were all up-regulated

Summary

Introduction

Microsporidia are a group of intracellular parasites that have recently been re-classified to fungi (Hirt et al, 1999; Han and Weiss, 2017). Microsporidia extrude the polar tube inside-out to inject sporoplasm into the host cells. The sporoplasm proliferates and form more new spores that will further infect surrounding cells (Weber et al, 1993; Meissner et al, 2012). Microsporidia infections could be local and restrained, yet systemic even fatal infections are not rare (Weber et al, 1994; Weiss, 1995; Meissner et al, 2012). Microsporidia spores may disseminate systemically via intravascular system (Anderson et al, 2019; Han et al, 2019), the mechanistic details of dissemination via circulatory system have not been fully examined

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