Liver sinusoidal endothelial cells contribute to the uptake and degradation of entero bacterial viruses.

Abstract:

:The liver is constantly exposed to dietary antigens, viruses, and bacterial products with inflammatory potential. For decades cellular uptake of virus has been studied in connection with infection, while the few studies designed to look into clearance mechanisms focused mainly on the role of macrophages. In recent years, attention has been directed towards the liver sinusoidal endothelial cells (LSECs), which play a central role in liver innate immunity by their ability to scavenge pathogen- and damage-associated molecular patterns. Every day our bodies are exposed to billions of gut-derived pathogens which must be efficiently removed from the circulation to prevent inflammatory and/or immune reactions in other vascular beds. Here, we have used GFP-labelled Enterobacteria phage T4 (GFP-T4-phage) as a model virus to study the viral scavenging function and metabolism in LSECs. The uptake of GFP-T4-phages was followed in real-time using deconvolution microscopy, and LSEC identity confirmed by visualization of fenestrae using structured illumination microscopy. By combining these imaging modalities with quantitative uptake and inhibition studies of radiolabelled GFP-T4-phages, we demonstrate that the bacteriophages are effectively degraded in the lysosomal compartment. Due to their high ability to take up and degrade circulating bacteriophages the LSECs may act as a primary anti-viral defence mechanism.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Øie CI,Wolfson DL,Yasunori T,Dumitriu G,Sørensen KK,McCourt PA,Ahluwalia BS,Smedsrød B

doi

10.1038/s41598-020-57652-0

subject

Has Abstract

pub_date

2020-01-21 00:00:00

pages

898

issue

1

issn

2045-2322

pii

10.1038/s41598-020-57652-0

journal_volume

10

pub_type

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