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Innate Immunity of Human Pancreatic Islets Infected with Different Enterovirus Types

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Diabetes and Viruses

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Abstract

Human enterovirus (HEV) infections are believed to be an environmental factor in the pathogenesis of type 1 diabetes pathogenesis, but the exact mechanism behind beta-cell death still remains unclear. Accumulating evidence suggests that viral induction of cytokines and chemokines promoting insulitis could be the link between virus infection and type 1 diabetes. When isolated human pancreatic islets are infected with HEV, IP-10 and MCP-1 are secreted from the islets. HEV infection of human islets induces many genes involved in the innate immune response or sensing viral dsRNA such as IL-6, IL-8, RANTES and INF-b, TLR3 and MDA5. If these proteins were expressed in the pancreas, they would promote b-cell death, directly or indirectly by attracting immune cells. Enterovirus-positive pancreatic sections from recent-onset type 1 diabetes cases also expressed the IP10 chemokine. T cells infiltrating the same areas expressed CXCR3, the IP10 receptor. In pancreatic sections from type 1 diabetes patients at onset stained positive for HEV protein 1 IP-10 was detected and, in addition, CCXCR3 was expressed on islet infiltrating was T-cells. These findings support the idea of HEV infection as a trigger of the immune-mediated beta-cell destruction and also suggest a possible mechanism for HEV-induced type 1 diabetes. The induction and secretion of the chemokine IP-10 with a prominent role in the induction of insulitis might be one of the key targets for immune intervention in this group of patients.

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Authors and Affiliations

  1. Department of Women’s and Children’s Health, Uppsala University, Akademiska Hospital, 75185, Uppsala, Sweden

    Gun Frisk Ph.D.

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  1. Gun Frisk Ph.D.
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Correspondence to Gun Frisk Ph.D. .

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Editors and Affiliations

  1. Queen Mary's School of Medicine and Dent, Centre for Diabetes & Metabolic Medicine, Institute of Cell & Molecular Science, n/a, London, E1 2AT, United Kingdom

    Keith Taylor

  2. Tampere University Hospital, Department of Virology, University of Tampere, n/a, Tampere, 33520, Finland

    Heikki Hyöty

  3. University of Insubria & Ospedale di Cir, Varese, Italy

    Antonio Toniolo

  4. University College London Medical School, n/a, London, NW3 2PF, United Kingdom

    Arie J. Zuckerman

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Frisk, G. (2013). Innate Immunity of Human Pancreatic Islets Infected with Different Enterovirus Types. In: Taylor, K., Hyöty, H., Toniolo, A., Zuckerman, A. (eds) Diabetes and Viruses. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4051-2_29

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