IL-12 receptor beta 1 and Toll-like receptor 4 increase IL-1 beta- and IL-18-associated myocarditis and coxsackievirus replication.
J Immunol
; 170(9): 4731-7, 2003 May 01.
Article
em En
| MEDLINE
| ID: mdl-12707353
ABSTRACT
Th1-type immune responses, mediated by IL-12-induced IFN-gamma, protect the host from most viral infections. To investigate the role of IL-12 and IFN-gamma on the development of Coxsackievirus B3 (CB3)-induced myocarditis, we examined the level of inflammation, viral replication, and cytokine production in IL-12Rbeta1- and IFN-gamma-deficient mice following CB3 infection. We report that IL-12Rbeta1 deficiency results in decreased viral replication and inflammation in the heart, while IFN-gamma deficiency exacerbates CB3 replication. Importantly, decreased IL-1beta and IL-18 levels in IL-12Rbeta1-deficient hearts correlated directly with decreased myocardial inflammation. Because IL-1beta and IL-18 were associated with myocardial inflammation, we examined the effect of TLR4 deficiency on CB3 infection and myocarditis. We found that TLR4-deficient mice also had significantly reduced levels of myocarditis, viral replication, and IL-1beta/IL-18, just as we had observed in IL-12Rbeta1-deficient mice. This is the first report that TLR4 influences CB3 replication. These results show that IL-12Rbeta1 and TLR4 exacerbate CB3 infection and myocarditis while IFN-gamma protects against viral replication. The remarkable similarities between the effects of IL-12Rbeta1 and TLR4 suggest that these receptors share common downstream pathways that directly influence IL-1beta and IL-18 production, and confirm that IL-1beta and IL-18 play a significant role in the pathogenesis of CB3-induced myocarditis. These findings have important implications not only for the pathogenesis of myocarditis, but for other autoimmune diseases triggered by viral infections.
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Bases de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
Glicoproteínas de Membrana
/
Regulação para Cima
/
Interleucina-1
/
Receptores de Interleucina
/
Enterovirus Humano B
/
Receptores de Superfície Celular
/
Interleucina-18
/
Miocardite
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos