Affordable Access

Access to the full text

Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes

Authors
  • Pane, Jessica A.1
  • Coulson, Barbara S.1
  • 1 The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, 792 Elizabeth Street, Melbourne, VIC, 3010, Australia , Melbourne (Australia)
Type
Published Article
Journal
Diabetologia
Publisher
Springer-Verlag
Publication Date
Mar 21, 2015
Volume
58
Issue
6
Pages
1149–1159
Identifiers
DOI: 10.1007/s00125-015-3562-3
Source
Springer Nature
Keywords
License
Yellow

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.

Report this publication

Statistics

Seen <100 times