title: Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells.
abstract: Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring 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.
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Marroqui
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lopes
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Reinaldo S
authors.initials: RS
authors.lastname: dos Santos
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Grieco
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Roivainen
authors.affiliation: Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Richardson
authors.affiliation: Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Op de Beeck
authors.affiliation: ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Decio L
authors.initials: DL
authors.lastname: Eizirik
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000821:virology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050416:Glucagon-Secreting Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000821:virology*; D017208:Rats, Wistar
keywords: apoptosis; cell biology; cytokines; diabetes mellitus; human; immunology; mouse; pancreatic alpha cell; pancreatic beta cell; rat; virus and diabetes; viruses