Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling
AuthorPane, JA; Fleming, FE; Graham, KL; Thomas, HE; Kay, TWH; Coulson, BS
Source TitleScientific Reports
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sCoulson, Barbara; Fleming, Fiona; Kay, Thomas; Graham, Kate; Neil, Jessica
AffiliationMicrobiology and Immunology
Medicine and Radiology
Document TypeJournal Article
CitationsPane, J. A., Fleming, F. E., Graham, K. L., Thomas, H. E., Kay, T. W. H. & Coulson, B. S. (2016). Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep29697.
Access StatusOpen Access
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-dependent gene expression, particularly within lymph nodes. The requirement for type I interferon signalling was analysed using NOD mice lacking a functional type I interferon receptor (NOD.IFNAR1(-/-) mice). Compared with NOD mice, NOD.IFNAR1(-/-) mice showed 8-fold higher RRV titers in lymph nodes and 3-fold higher titers of total RRV antibody in serum. However, RRV-infected NOD.IFNAR1(-/-) mice exhibited delayed pDC and lymphocyte activation, no T helper 1 bias in RRV-specific antibodies and unaltered diabetes onset when compared with uninfected controls. Thus, the type I interferon signalling induced by RRV infection is required for bystander lymphocyte activation and accelerated type 1 diabetes onset in genetically susceptible mice.
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