Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells

  1. Laura Marroqui Esclapez
  2. Miguel Lopes
  3. Reinaldo S dos Santos
  4. Fabio A Grieco
  5. Merja Roivainen
  6. Sarah J Richardson
  7. Noel G Morgan
  8. Anne Op de beeck
  9. Decio L Eizirik  Is a corresponding author
  1. Universite Libre de Bruxelles, Belgium
  2. National Institute for Health and Welfare, Finland
  3. University of Exeter Medical School, United Kingdom

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighbouring α cells are preserved. Viral infections by Coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We presently describe that global gene expression is similar in cytokine-treated and virus-infected human islet cells, with up-regulation of gene networks involved in cell autonomous immune responses. Comparison between the responses of rat pancreatic α and β cells to infection by CVB5 and 4 indicate that α cells trigger a more efficient antiviral response than β cells, including higher basal and induced expression of STAT1-regulated genes, and are thus better able to clear viral infections than β cells. These differences may explain why pancreatic β cells, but not α cells, are targeted by an autoimmune response during T1D.

Article and author information

Author details

  1. Laura Marroqui Esclapez

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Miguel Lopes

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  3. Reinaldo S dos Santos

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Fabio A Grieco

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Merja Roivainen

    National Institute for Health and Welfare, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  6. Sarah J Richardson

    Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Noel G Morgan

    Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Anne Op de beeck

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  9. Decio L Eizirik

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium
    For correspondence
    deizirik@ulb.ac.be
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Male Wistar rats (Charles River Laboratories, L'Arbresle Cedex, France) were housed and used according to the guidelines of the Belgian Regulations for Animal Care, with the approval by the local Ethical Committee (protocol number 465N; period of validity 07/2013-07/2017).

Human subjects: Human islets were isolated from 2 non-diabetic organ donors with approval from the local Ethical Committee in Pisa, Italy. Organ and tissue donation in Italy is regulated by the art. 23 of the national law n. 91, issued on April 1st, 1999; in Tuscany the regional transplant organization (OTT, Organizzazione Toscana Trapianti) allows that organs not suitable for clinical transplantation are used for research purposes provided informed consent has been signed by the responsible relative. Prof. Marchetti's group has access to donated pancreases for the preparation and study of isolated islets on the basis of approval by their local ethics committee, renewed in 2013.

Reviewing Editor

  1. Mark McCarthy, Oxford University, United Kingdom

Publication history

  1. Received: February 14, 2015
  2. Accepted: June 8, 2015
  3. Accepted Manuscript published: June 10, 2015 (version 1)
  4. Version of Record published: June 25, 2015 (version 2)

Copyright

© 2015, Marroqui Esclapez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Laura Marroqui Esclapez
  2. Miguel Lopes
  3. Reinaldo S dos Santos
  4. Fabio A Grieco
  5. Merja Roivainen
  6. Sarah J Richardson
  7. Noel G Morgan
  8. Anne Op de beeck
  9. Decio L Eizirik
(2015)
Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells
eLife 4:e06990.
https://doi.org/10.7554/eLife.06990
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