Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of coxsackievirus B3-induced myocarditis and influences type I interferon production

Article

关键词: TOLL-LIKE RECEPTORS;    DOUBLE-STRANDED-RNA;    NF-KAPPA-B;    ADENOVIRUS RECEPTOR;    MYD88-DEFICIENT MICE;    CUTTING EDGE;    INFECTION;    RECOGNITION;    MYD88;    ACTIVATION;   

DOI  :  10.1161/CIRCULATIONAHA.105.536433

来源: SCIE

【 摘 要 】

Background - Myeloid differentiation factor (MyD)-88 is a key adaptor protein that plays a major role in the innate immune pathway. How MyD88 may regulate host response in inflammatory heart disease is unknown. Methods and Results - We found that the cardiac protein level of MyD88 was significantly increased in the hearts of wild-type mice after exposure to Coxsackievirus B3 (CVB3). MyD88(-/-) mice showed a dramatic higher survival rate (86%) in contrast to the low survival (35%) in the MyD88(-/-) mice after CVB3 infection (P < 0.0001). Pathological examination showed a significant decrease of cardiac and pancreatic inflammation in the MyD88(-/-) mice. Viral concentrations in the hearts were significantly decreased in the MyD88(-/-) mice. Cardiac mRNA levels for interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and IL-18 were significantly decreased in the MyD88(-/-) mice. Similarly, serum levels of T-helper 1 cytokines were significantly decreased in the MyD88(-/-) mice. In contrast, cardiac protein levels of the activated interferon regulatory factor (IRF)-3 and IFN-beta were significantly increased in the MyD88(-/-) mice but not other usual upstream signals to IRF-3. The cardiac expression of coxsackie-adenoviral receptor and p56(lck) were also significantly decreased. Conclusions - MyD88 appears to be a key contributor to cardiac inflammation, mediating cytokine production and T-helper-1/2 cytokine balance, increasing coxsackie-adenoviral receptor and p56(lck) expression and viral titers after CVB3 exposure. Absence of MyD88 confers host protection possibly through novel direct activation of IRF-3 and IFN-beta.

【 授权许可】

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