Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease
Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR)3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3) myocarditis in mice. Although TLR3- or TRIF-deficient mice developed si...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/129486 |
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| author | Eric D. Abston Michael J. Coronado Adriana Bucek Djahida Bedja Jaewook Shin Joseph B. Kim Eunyong Kim Kathleen L. Gabrielson Dimitrios Georgakopoulos Wayne Mitzner DeLisa Fairweather |
| author_facet | Eric D. Abston Michael J. Coronado Adriana Bucek Djahida Bedja Jaewook Shin Joseph B. Kim Eunyong Kim Kathleen L. Gabrielson Dimitrios Georgakopoulos Wayne Mitzner DeLisa Fairweather |
| author_sort | Eric D. Abston |
| collection | DOAJ |
| description | Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR)3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3) myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL)-4-dominant T helper (Th)2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis. |
| format | Article |
| id | doaj-art-0862b46840a04b689ed4cf0f2f3a7906 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-0862b46840a04b689ed4cf0f2f3a79062025-02-03T01:11:12ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/129486129486Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic DiseaseEric D. Abston0Michael J. Coronado1Adriana Bucek2Djahida Bedja3Jaewook Shin4Joseph B. Kim5Eunyong Kim6Kathleen L. Gabrielson7Dimitrios Georgakopoulos8Wayne Mitzner9DeLisa Fairweather10Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, 615 N. Wolfe Street, Baltimore, MD 21205, USACVRx Inc., 9201 West Broadway Avenue, Minneapolis, MN 55445, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USADepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USAViral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR)3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3) myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL)-4-dominant T helper (Th)2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.http://dx.doi.org/10.1155/2012/129486 |
| spellingShingle | Eric D. Abston Michael J. Coronado Adriana Bucek Djahida Bedja Jaewook Shin Joseph B. Kim Eunyong Kim Kathleen L. Gabrielson Dimitrios Georgakopoulos Wayne Mitzner DeLisa Fairweather Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease Clinical and Developmental Immunology |
| title | Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease |
| title_full | Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease |
| title_fullStr | Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease |
| title_full_unstemmed | Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease |
| title_short | Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease |
| title_sort | th2 regulation of viral myocarditis in mice different roles for tlr3 versus trif in progression to chronic disease |
| url | http://dx.doi.org/10.1155/2012/129486 |
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