Immune transcriptome of cells infected with enterovirus strains obtained from cases of type 1 diabetes

Anello Marcello Poma, Angelo Genoni, Francesco Broccolo, Maria Denaro, Alberto Pugliese, Fulvio Basolo, Antonio Toniolo

Research output: Contribution to journalArticle

Abstract

Enterovirus (EV) infection of insulin-producing pancreatic beta cells is associated with type 1 diabetes (T1D), but little is known about the mechanisms that lead the virus to cause a persistent infection and, possibly, to induce beta cell autoimmunity. A cell line susceptible to most enterovirus types was infected with EV isolates from cases of T1D and, for comparison, with a replication-competent strain of coxsackievirus B3. The transcription of immune-related genes and secretion of cytokines was evaluated in infected vs. uninfected cells. Acutely infected cells showed the preserved transcription of type I interferon (IFN) pathways and the enhanced transcription/secretion of IL6, IL8, LIF, MCP1, and TGFB1. On the other hand, infection by defective EV strains obtained from diabetic subjects suppressed IFN pathways and the transcription of most cytokines, while enhancing the expression of IL8, IL18, IL32, and MCP1. IL18 and IL32 are known for their pathogenic role in autoimmune diabetes. Thus, the cytokine profile of AV3 cells infected by diabetes-derived EV strains closely matches that observed in patients at the early stages of T1D. The concordance of our results with clinically verified information reinforces the hypothesis that the immune changes observed in type 1 diabetic patients are due to a hardly noticeable virus infection.

Original languageEnglish (US)
Article number1031
Pages (from-to)1-16
Number of pages16
JournalMicroorganisms
Volume8
Issue number7
DOIs
StatePublished - Jul 2020

Keywords

  • Autoimmunity
  • Cytokine
  • Diabetes
  • IL18
  • IL32
  • Interferon
  • MCP1
  • Pathogenesis
  • Persistent infection
  • Virus

ASJC Scopus subject areas

  • Microbiology
  • Virology
  • Microbiology (medical)

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