Toll-like receptor 4-induced cytokine production circumvents protection conferred by TGF-beta in coxsackievirus-mediated autoimmune myocarditis
Coxsackie B virus (CBV) infections are a leading cause of autoimmune myocarditis associated with inflammatory heart disease and sudden death in young adults. Previously, we demonstrated that transgenic expression of the immunosuppressive cytokine, transforming growth factor-beta (TGF-beta), specific...
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 121(2006), 3 vom: 01. Dez., Seite 339-49 |
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| Auteur principal: | |
| Autres auteurs: | , , |
| Format: | Article |
| Langue: | English |
| Publié: |
2006
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't Autoantibodies Cytokines Lipopolysaccharides Toll-Like Receptor 4 Transforming Growth Factors 76057-06-2 |
| Résumé: | Coxsackie B virus (CBV) infections are a leading cause of autoimmune myocarditis associated with inflammatory heart disease and sudden death in young adults. Previously, we demonstrated that transgenic expression of the immunosuppressive cytokine, transforming growth factor-beta (TGF-beta), specifically in the pancreas protected otherwise susceptible mice from CBV-mediated autoimmune myocarditis. Herein, we demonstrate that macrophages from these transgenic mice fail to upregulate the costimulatory molecule CD40 following infection, suggesting that pancreatic TGF-beta protects by limiting antigen stimulation. We further demonstrate that co-administration of LPS from Salmonella minnesota, a Toll-like receptor (TLR)-4 ligand, with CBV infection overcomes protection whereas the TLR-2 agonist, LPS from Porphyromonas gingivalis, does not. Furthermore, LPS-mediated disease induction correlates with increased levels of pro-inflammatory cytokines. Interestingly, the action of LPS (TLR-4) did not alter antibody isotype switching, increase viral replication or modulate CD40 expression. Instead, LPS breaks protection through an alternative mechanism specific to TLR-4 signaling |
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| Description: | Date Completed 05.01.2007 Date Revised 20.11.2006 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |