Journal article

Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling

Jessica A Pane, Fiona E Fleming, Kate L Graham, Helen E Thomas, Thomas WH Kay, Barbara S Coulson



Rotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naïve NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses. Here we demonstrate bystander lymphocyte activation in RRV-infected NOD mice, which showed pDC activation and strong upregulation of interferon-depende..

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Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

We thank David Taylor, Rhiannon Hall, Thomas Cumming and Rebecca Bowyer from the Biological Research Facility of the Department of Microbiology and Immunology at the University of Melbourne for mouse husbandry. We are grateful for the assistance of Nicole Webster and Nicole Gilbertson with regulatory T cell studies, Vi Dang with diabetes monitoring, and Gavan Holloway in providing helpful suggestions. This work was supported by Project Grants APP1044868 and APP1103279, and Senior Research Fellowship APP628319, to B.C. from the National Health and Medical Research Council of Australia.