Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes
- 21 March 2015
- journal article
- review article
- Published by Springer Science and Business Media LLC in Diabetologia
- Vol. 58 (6), 1149-1159
- https://doi.org/10.1007/s00125-015-3562-3
Abstract
Viruses are considered to be potential key modulators of type 1 diabetes mellitus, with several possible mechanisms proposed for their modes of action. Here we discuss the evidence for virus involvement, including pancreatic infection and the induction of T cell-mediated molecular mimicry. A particular focus of this review is the further possibility that virus infection triggers bystander activation of pre-existing autoreactive lymphocytes. In this scenario, the virus triggers dendritic cell maturation and proinflammatory cytokine secretion by engaging pattern recognition receptors. These proinflammatory cytokines provoke bystander autoreactive lymphocyte activation in the presence of cognate autoantigen, which leads to enhanced beta cell destruction. Importantly, this mechanism does not necessarily involve pancreatic virus infection, and its virally non-specific nature suggests that it might represent a means commonly employed by multiple viruses. The ability of viruses specifically associated with type 1 diabetes, including group B coxsackievirus, rotavirus and influenza A virus, to induce these responses is also examined. The elucidation of a mechanism shared amongst several viruses for accelerating progression to type 1 diabetes would facilitate the identification of important targets for disease intervention.Keywords
This publication has 109 references indexed in Scilit:
- Environmental Triggers of Type 1 DiabetesCold Spring Harbor Perspectives in Medicine, 2012
- Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patientsThe Journal of Experimental Medicine, 2012
- Pre-existing autoimmunity determines type 1 diabetes outcome after Flt3-ligand treatmentJournal of Autoimmunity, 2010
- Rare Variants of IFIH1 , a Gene Implicated in Antiviral Responses, Protect Against Type 1 DiabetesScience, 2009
- Type 1 diabetes patients have significantly lower frequency of plasmacytoid dendritic cells in the peripheral bloodClinical Immunology, 2008
- IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cellsHuman Molecular Genetics, 2008
- Innate immunity and intestinal microbiota in the development of Type 1 diabetesNature, 2008
- Interferon-α initiates type 1 diabetes in nonobese diabetic miceProceedings of the National Academy of Sciences of the United States of America, 2008
- Rotavirus Infection of Infant and Young Adult Nonobese Diabetic Mice Involves Extraintestinal Spread and Delays Diabetes OnsetJournal of Virology, 2007
- Toll-like receptor signallingNature Reviews Immunology, 2004