Transforming growth factor-β inhibits coxsackievirus-mediated autoimmune myocarditis

Marc S. Horwitz, Maria Knudsen, Alex Ilic, Cody Fine, Nora Sarvetnick

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Clinical myocarditis is a precursor to dilated cardiomyopathy and a principal cause of heart failure. Nearly 30% of all recently diagnosed cases of myocarditis are attributable to infection with coxsackie B virus (CBV), the most frequently associated pathogen. CBV initially replicates in the pancreas and quickly spreads to the heart, inducing chronic autoimmunity. To determine whether immunosuppressive cytokines could act to limit the extent of autoimmunity to the heart, we infected transgenic mice that express immunosuppressive cytokines in the pancreas. Herein, we demonstrate that transgenic expression of transforming growth factor-β1 (TGF-β) within the pancreatic beta cells prevented mice from developing autoimmune myocarditis after CBV infection. In contrast, transgenic expression of interleukin-4 did not inhibit virus-mediated heart disease. Furthermore, we show that TGF-β expression reduced viral replication while promoting the recruitment of macrophages into the pancreas. These results illustrate the benefit of TGF-β in controlling not only viral replication, but also CBV-mediated autoimmunity.

Original languageEnglish (US)
Pages (from-to)722-733
Number of pages12
JournalViral Immunology
Volume19
Issue number4
DOIs
StatePublished - Jan 1 2006

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ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology

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