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  • Review Article
  • Published:

Viral infections in type 1 diabetes mellitus — why the β cells?

Nature Reviews Endocrinology volume 12, pages 263–273 (2016)Cite this article

Subjects

Key Points

  • Viral infections — particularly by enteroviruses (for example, coxsackievirus) — have been implicated in the development of type 1 diabetes mellitus (T1DM)

  • Many candidate genes for T1DM regulate antiviral responses in pancreatic β cells

  • Pancreatic islet α cells trigger a more efficient antiviral response than β cells following infection with diabetogenic viruses, thus enabling α cells to eradicate viral infections without undergoing apoptosis

  • An inability to clear viral infections could explain why chronically infected β cells, but not α cells, are targeted by an autoimmune response and killed during development of T1DM

  • The identification of key diabetogenic viruses and the downstream mechanisms leading to insulitis might enable a preventive approach to T1DM by vaccination

Abstract

Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection — particularly by enteroviruses (for example, coxsackievirus) — as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.

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Figure 1: Regulation of key antiviral responses in pancreatic β cells.
Figure 2: Crosstalk between viral infection, genetic background and early education of the immune system.
Figure 3: Differential autonomous antiviral response determines the outcome of infection in pancreatic α cells and β cells.

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Acknowledgements

The research by A.O.d.B. and D.L.E. that is discussed in this Review was supported by the Belgian Fonds National de la Recherche Scientifique (FNRS; grants T.0036.13 and FRFS-Welbio CR-2015A-06); the European Union (projects Naimit and BetaBat in the Seventh Framework Programme of the European Commission); the Juvenile Diabetes Foundation; the Helmsley Type 1 Diabetes Program; and the NIH–NIDDK–HIRN Consortium. A.O.d.B. and D.L.E. also receive support from the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by the Juvenile Diabetes Research Foundation International (JDRF). Organ procurement organisations partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/our-partners.php. F. Grieco (Center for Diabetes Research, Universite Libre de Bruxelles, Belgium) provided the micrographs shown in Fig. 3.

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  1. Center for Diabetes Research, Universite Libre de Bruxelles, 808 Route de Lennik, CP618, Brussels, B-1070, Belgium

    Anne Op de Beeck & Decio L. Eizirik

  2. Welbio, Universite Libre de Bruxelles, 808 Route de Lennik, CP618, Brussels, B-1070, Belgium

    Decio L. Eizirik

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  1. Anne Op de Beeck
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Op de Beeck, A., Eizirik, D. Viral infections in type 1 diabetes mellitus — why the β cells?. Nat Rev Endocrinol 12, 263–273 (2016). https://doi.org/10.1038/nrendo.2016.30

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