High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier
- University of Queensland, Australia
- Translational Research Institute, Australia
Abstract
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.
Data availability
RNA sequencing data generated in this study are available on the Gene Expression Omnibus repository with accession number GSE145232.
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High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrierNCBI Gene Expression Omnibus, GSE145232.
Article and author information
Author details
Kirsty Renfree Short
Funding
National Health and Medical Research Council ((APP1159959)
- Kirsty Renfree Short
National Health and Medical Research Council
- Linda A Gallo
National Health and Medical Research Council (DE180100512)
- Kyle R Upton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were approved by the University of Queensland Animal Ethics Committee. (permit no. 071/17).
Copyright
© 2020, Hulme et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier
eLife 9:e56907.
https://doi.org/10.7554/eLife.56907
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