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

eLife - Tập 9
Katina D. Hulme1, Limin Yan1, Rebecca J Marshall1, Conor J. Bloxham2, Kyle R. Upton1, Sumaira Z. Hasnain3,4, Helle Bielefeldt‐Ohmann5,1, Zhixuan Loh6, Katharina Ronacher5,3,4, Keng Yih Chew1, Linda A. Gallo3,2,4, Kirsty R. Short5,1
1School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Australia
2School of Biomedical Sciences, The University of Queensland, Woolloongabba, Australia;
3Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia
4Translational Research Institute, Woolloongabba, Australia
5Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Australia
6Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia

Tóm tắt

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.

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