Myeloid Differentiation Factor-88 Plays a Crucial Role in the Pathogenesis of Coxsackievirus B3–Induced Myocarditis and Influences Type I Interferon Production

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Abstract
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)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, 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 protei...