School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia
Limin Yan
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia
Rebecca J Marshall
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia
Conor J Bloxham
School of Biomedical Sciences, The University of Queensland, Woolloongabba, Australia
Kyle R Upton
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia
Sumaira Z Hasnain
Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia
Helle Bielefeldt-Ohmann
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Australia
Zhixuan Loh
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia
Katharina Ronacher
Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Australia
Keng Yih Chew
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia
Linda A Gallo
School of Biomedical Sciences, The University of Queensland, Woolloongabba, Australia; Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Australia
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.
