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

Diabetologia
Jessica A Pane, Barbara S Coulson

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 dia...Continue Reading

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Mar 30, 2016·Nature Reviews. Endocrinology·Anne Op de Beeck, Decio L Eizirik
Aug 2, 2017·The Journal of Clinical Investigation·Alberto Pugliese
Dec 13, 2019·Experimental & Molecular Medicine·Tae-Shin Kim, Eui-Cheol Shin
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Aug 8, 2021·Microorganisms·Sonia R IsaacsKi Wook Kim

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