ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2013
TLR3 deficiency induces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Sex differences in a mouse model of radiation-induced cardiomyopathy.Biology of sex differences · 2026Article
- Mapping myocarditis in three dimensions.Cardiovascular research · 2025Article
- Toll-like receptor 3: a double-edged sword.Biomarker research · 2025Review
- Sex differences in mitochondrial gene expression during viral myocarditis.Biology of sex differences · 2024Article
- Enterovirus-D68 - A Reemerging Non-Polio Enterovirus that Causes Severe Respiratory and Neurological Disease in Children.Frontiers in virology (Lausanne, Switzerland) · 2024Article
- The inflammatory spectrum of cardiomyopathies.Frontiers in cardiovascular medicine · 2024Review
- Sex differences in mitochondrial gene expression during viral myocarditis.Research square · 2023Article
- Sex differences in left-ventricular strain in a murine model of coxsackievirus B3 myocarditis.iScience · 2023Article
- Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice.Small (Weinheim an der Bergstrasse, Germany) · 2023Article
- The Molecular Role of Immune Cells in Dilated Cardiomyopathy.Medicina (Kaunas, Lithuania) · 2023Review
- Toll-like receptors in cardiac hypertrophy.Frontiers in cardiovascular medicine · 2023Review
- Sex and gender differences in myocarditis and dilated cardiomyopathy: An update.Frontiers in cardiovascular medicine · 2023Review
- Role of Toll-Like Receptors and Th Responses in Viral Myocarditis.Frontiers in immunology · 2022Review
- Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses.Journal of Zhejiang University. Science. B · 2021Review
- Sex Differences, Genetic and Environmental Influences on Dilated Cardiomyopathy.Journal of clinical medicine · 2021Review
- RNA Signaling in Pulmonary Arterial Hypertension-A Double-Stranded Sword.International journal of molecular sciences · 2020Review
- Interleukin 4: Its Role in Hypertension, Atherosclerosis, Valvular, and Nonvalvular Cardiovascular Diseases.Journal of cardiovascular pharmacology and therapeutics · 2020Review
- Toll-like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2019Article
- Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology.Cardiovascular research · 2018Review
- The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC.European journal of heart failure · 2018Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Recent findings indicate that TLR3 polymorphisms increase susceptibility to enteroviral myocarditis and inflammatory dilated cardiomyopathy (iDCM) in patients. TLR3 signaling has been found to inhibit coxsackievirus B3 (CVB3) replication and acute myocarditis in mouse models, but its role in the progression from myocarditis to iDCM has not been previously investigated. In this study we found that TLR3 deficiency increased acute (P = 5.9 × 10(-9)) and chronic (P = 6.0 × 10(-7)) myocarditis compared with WT B6.129, a mouse strain that is resistant to chronic myocarditis and iDCM. Using left ventricular in vivo hemodynamic assessment, we found that TLR3-deficient mice developed progressively worse chronic cardiomyopathy. TLR3 deficiency significantly increased viral replication in the heart during acute myocarditis from day 3 through day 12 after infection, but infectious virus was not detected in the heart during chronic disease. TLR3 deficiency increased cytokines associated with a T helper (Th)2 response, including IL-4 (P = 0.03), IL-10 (P = 0.008), IL-13 (P = 0.002), and TGF-β(1) (P = 0.005), and induced a shift to an immunoregulatory phenotype in the heart. However, IL-4-deficient mice had improved heart function during acute CVB3 myocarditis by echocardiography and in vivo hemodynamic assessment compared with wild-type mice, indicating that IL-4 impairs cardiac function during myocarditis. IL-4 deficiency increased regulatory T-cell and macrophage populations, including FoxP3(+) T cells (P = 0.005) and Tim-3(+) macrophages (P = 0.004). Thus, TLR3 prevents the progression from myocarditis to iDCM following CVB3 infection by reducing acute viral replication and IL-4 levels in the heart.
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