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

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.

SUBMITTER: Hulme KD

PROVIDER: S-EPMC7392605 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Hulme Katina D KD Yan Limin L Marshall Rebecca J RJ Bloxham Conor J CJ Upton Kyle R KR Hasnain Sumaira Z SZ Bielefeldt-Ohmann Helle H Loh Zhixuan Z Ronacher Katharina K Chew Keng Yih KY Gallo Linda A LA Short Kirsty R KR

eLife 20200722

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-induc ...[more]

PMID: 32697191

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

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

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