title: Interferons induce an antiviral state in human pancreatic islet cells.
abstract: Enterovirus infections, in particular those with Coxsackieviruses, have been linked to the development of type 1 diabetes (T1D). Although animal models have demonstrated that interferons (IFNs) regulate virus-induced T1D by acting directly on the beta cell, little is known on the human pancreatic islet response to IFNs. Here we show that human islet cells respond to IFNs by expressing signature genes of antiviral defense. We also demonstrate that they express three intracellular sensors for viral RNA, the toll like receptor 3 (TLR3) gene, the retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation-associated gene-5 (MDA-5), which induce type I IFN production in infected cells. Finally, we show for the first time that the IFN-induced antiviral state provides human islets with a powerful protection from the replication of Coxsackievirus. This may be critical for beta cell survival and protection from virus-induced T1D in humans.
authors.affiliation: Center for Infectious Medicine F59, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden. Monica.Hultcrantz@ki.se
authors.forename: Monica
authors.initials: M
authors.lastname: Hultcrantz
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hühn
authors.forename: Monika
authors.initials: M
authors.lastname: Wolf
authors.forename: Annika
authors.initials: A
authors.lastname: Olsson
authors.forename: Stella
authors.initials: S
authors.lastname: Jacobson
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Williams
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Malin
authors.initials: M
authors.lastname: Flodström-Tullberg
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D003384:Coxsackievirus Infections / Q000276:immunology / Q000821:virology; D029822:Enterovirus B, Human / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011506:Proteins; D007371:Interferon-gamma