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 Citations (Scopus)

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

Fingerprint

Human Enterovirus B
Enterovirus
Myocarditis
Transforming Growth Factors
Autoimmunity
Pancreas
Immunosuppressive Agents
Coxsackievirus Infections
Cytokines
Insulin-Secreting Cells
Dilated Cardiomyopathy
Interleukin-4
Transgenic Mice
Heart Diseases
Heart Failure
Macrophages
Viruses
Infection

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology

Cite this

Transforming growth factor-β inhibits coxsackievirus-mediated autoimmune myocarditis. / Horwitz, Marc S.; Knudsen, Maria; Ilic, Alex; Fine, Cody; Sarvetnick, Nora.

In: Viral Immunology, Vol. 19, No. 4, 01.01.2006, p. 722-733.

Research output: Contribution to journalArticle

Horwitz, Marc S. ; Knudsen, Maria ; Ilic, Alex ; Fine, Cody ; Sarvetnick, Nora. / Transforming growth factor-β inhibits coxsackievirus-mediated autoimmune myocarditis. In: Viral Immunology. 2006 ; Vol. 19, No. 4. pp. 722-733.
@article{a2184b3f46eb4c7880fb7c5e9c79eaff,
title = "Transforming growth factor-β inhibits coxsackievirus-mediated autoimmune myocarditis",
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.",
author = "Horwitz, {Marc S.} and Maria Knudsen and Alex Ilic and Cody Fine and Nora Sarvetnick",
year = "2006",
month = "1",
day = "1",
doi = "10.1089/vim.2006.19.722",
language = "English (US)",
volume = "19",
pages = "722--733",
journal = "Viral Immunology",
issn = "0882-8245",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - Transforming growth factor-β inhibits coxsackievirus-mediated autoimmune myocarditis

AU - Horwitz, Marc S.

AU - Knudsen, Maria

AU - Ilic, Alex

AU - Fine, Cody

AU - Sarvetnick, Nora

PY - 2006/1/1

Y1 - 2006/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33846083900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846083900&partnerID=8YFLogxK

U2 - 10.1089/vim.2006.19.722

DO - 10.1089/vim.2006.19.722

M3 - Article

C2 - 17201667

AN - SCOPUS:33846083900

VL - 19

SP - 722

EP - 733

JO - Viral Immunology

JF - Viral Immunology

SN - 0882-8245

IS - 4

ER -