Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication

Myocarditis is an inflammatory disease caused by viral infection. Different subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac inflammation associated with myocyte loss and remodeling. Here, we study possible cell sources for viral replication using three compartments o...

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Main Authors: Diana Lindner, Jia Li, Konstantinos Savvatis, Karin Klingel, Stefan Blankenberg, Carsten Tschöpe, Dirk Westermann
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/519528
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author Diana Lindner
Jia Li
Konstantinos Savvatis
Karin Klingel
Stefan Blankenberg
Carsten Tschöpe
Dirk Westermann
author_facet Diana Lindner
Jia Li
Konstantinos Savvatis
Karin Klingel
Stefan Blankenberg
Carsten Tschöpe
Dirk Westermann
author_sort Diana Lindner
collection DOAJ
description Myocarditis is an inflammatory disease caused by viral infection. Different subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac inflammation associated with myocyte loss and remodeling. Here, we study possible cell sources for viral replication using three compartments of the heart: fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j mice with Coxsackievirus B3 (CVB3) and detected increased gene expression of anti-inflammatory and antiviral cytokines in the heart. Subsequently, we infected cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due to viral infection, the expression of TNF-α, IL-6, MCP-1, and IFN-β was significantly increased in cardiac fibroblasts compared to cardiomyocytes or macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts were infected by CVB3 and displayed a higher virus replication (132-fold increase) compared to cardiomyocytes (14-fold increase) between 6 and 24 hours after infection. At higher virus concentrations, macrophages are able to reduce the viral copy number. At low virus concentration a persistent virus infection was determined. Therefore, we suggest that cardiac fibroblasts play an important role in the pathology of CVB3-induced myocarditis and are another important contributor of virus replication aggravating myocarditis.
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series Mediators of Inflammation
spelling doaj-art-8f292efef64349afa482a05a50e112e92025-08-20T03:36:58ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/519528519528Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 ReplicationDiana Lindner0Jia Li1Konstantinos Savvatis2Karin Klingel3Stefan Blankenberg4Carsten Tschöpe5Dirk Westermann6Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, GermanyClinic for General and Interventional Cardiology, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, GermanyDepartment of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Berlin, GermanyDepartment of Molecular Pathology, Institute for Pathology, Eberhard Karls University of Tübingen, Tübingen, GermanyClinic for General and Interventional Cardiology, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, GermanyDepartment of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Berlin, GermanyClinic for General and Interventional Cardiology, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, GermanyMyocarditis is an inflammatory disease caused by viral infection. Different subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac inflammation associated with myocyte loss and remodeling. Here, we study possible cell sources for viral replication using three compartments of the heart: fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j mice with Coxsackievirus B3 (CVB3) and detected increased gene expression of anti-inflammatory and antiviral cytokines in the heart. Subsequently, we infected cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due to viral infection, the expression of TNF-α, IL-6, MCP-1, and IFN-β was significantly increased in cardiac fibroblasts compared to cardiomyocytes or macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts were infected by CVB3 and displayed a higher virus replication (132-fold increase) compared to cardiomyocytes (14-fold increase) between 6 and 24 hours after infection. At higher virus concentrations, macrophages are able to reduce the viral copy number. At low virus concentration a persistent virus infection was determined. Therefore, we suggest that cardiac fibroblasts play an important role in the pathology of CVB3-induced myocarditis and are another important contributor of virus replication aggravating myocarditis.http://dx.doi.org/10.1155/2014/519528
spellingShingle Diana Lindner
Jia Li
Konstantinos Savvatis
Karin Klingel
Stefan Blankenberg
Carsten Tschöpe
Dirk Westermann
Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication
Mediators of Inflammation
title Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication
title_full Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication
title_fullStr Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication
title_full_unstemmed Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication
title_short Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication
title_sort cardiac fibroblasts aggravate viral myocarditis cell specific coxsackievirus b3 replication
url http://dx.doi.org/10.1155/2014/519528
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