High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier

Katina D Hulme; Limin Yan; Rebecca J Marshall; Conor J Bloxham; Kyle R Upton; Sumaira Z Hasnain; Helle Bielefeldt-Ohmann; Zhixuan Loh; Katharina Ronacher; Keng Yih Chew; Linda A Gallo; Kirsty R Short

doi:10.7554/eLife.56907

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High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier

Journal article

Open access

Peer reviewed

High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier

Katina D Hulme, Limin Yan, Rebecca J Marshall, Conor J Bloxham, Kyle R Upton, Sumaira Z Hasnain, Helle Bielefeldt-Ohmann, Zhixuan Loh, Katharina Ronacher, Keng Yih Chew, …

eLife, Vol.9, pp.1-20

2020

DOI: https://doi.org/10.7554/eLife.56907

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Abstract

Animals

Endothelial Cells - physiology

Epithelial Cells - physiology

Humans

Influenza A virus - physiology

Influenza, Human - virology

Mice

Mice, Inbred C57BL

Diabetes mellitus is a known susceptibility factor for severe influenza virus infections. However, the mechanisms that underlie this susceptibility remain incompletely understood. Here, the effects of high glucose levels on influenza severity were investigated using an in vitro model of the pulmonary epithelial-endothelial barrier as well as an in vivo murine model of type II diabetes. In vitro we show that high glucose conditions prior to IAV infection increased virus-induced barrier damage. This was associated with an increased pro-inflammatory response in endothelial cells and the subsequent damage of the epithelial junctional complex. These results were subsequently validated in vivo. This study provides the first evidence that hyperglycaemia may increase influenza severity by damaging the pulmonary epithelial-endothelial barrier and increasing pulmonary oedema. These data suggest that maintaining long-term glucose control in individuals with diabetes is paramount in reducing the morbidity and mortality associated with influenza virus infections.

Details

Title: High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier
Authors: Katina D Hulme (Author) - The University of Queensland
Limin Yan (Author) - The University of Queensland
Rebecca J Marshall (Author) - The University of Queensland
Conor J Bloxham (Author) - The University of Queensland
Kyle R Upton (Author) - The University of Queensland
Sumaira Z Hasnain (Author) - The University of Queensland
Helle Bielefeldt-Ohmann (Author) - The University of Queensland
Zhixuan Loh (Author) - The University of Queensland
Katharina Ronacher (Author) - The University of Queensland
Keng Yih Chew (Author) - The University of Queensland
Linda A Gallo (Author) - The University of Queensland
Kirsty R Short (Author) - The University of Queensland
Publication details: eLife, Vol.9, pp.1-20
Publisher: eLife Sciences Publications Ltd
Date published: 2020
DOI: 10.7554/eLife.56907
ISSN: 2050-084X
Copyright note: Copyright Hulme et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99620607802621
Output Type: Journal article

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