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TRIF Is a Critical Survival Factor in Viral Cardiomyopathy

2011; American Association of Immunologists; Volume: 186; Issue: 4 Linguagem: Inglês

10.4049/jimmunol.1002029

1550-6606

Alexander Riad, Dirk Westermann, Christin Zietsch, Konstantinos Savvatis, Peter Moritz Becher, Stefan Bereswill, Markus M. Heimesaat, Olga Lettau, Dirk Laßner, Andrea Dörner, Wolfgang Poller, M. Busch, Stephan B. Felix, Heinz‐Peter Schultheiß, Carsten Tschöpe,

RNA regulation and disease

Abstract TRIF is a member of the innate immune system known to be involved in viral recognition and type I IFN activation. Because IFNs are thought to play an important role in viral myocarditis, we investigated the role of TRIF in induced myocarditis in mice. Whereas C57BL/6 (wild-type) mice showed only mild myocarditis, including normal survival postinfection with coxsackievirus group B serotype 3 (CVB3), infection of TRIF−/− mice led to the induction of cardiac remodeling, severe heart failure, and 100% mortality (p < 0.0001). These mice showed markedly reduced virus control in cardiac tissues and cardiomyocytes. This was accompained with dynamic cardiac cytokine activation in the heart, including a suppression of the antiviral cytokine IFN-β in the early viremic phase. TRIF−/− myocytes displayed a TLR4-dependent suppression of IFN-β, and pharmacological treatment of CVB3-infected TRIF−/− mice with murine IFN-β led to improved virus control and reduced cardiac inflammation. Additionally, this treatment within the viremic phase of myocarditis showed a significant long-term outcome indexed by reduced mortality (20 versus 100%; p < 0.001). TRIF is essential toward a cardioprotection against CVB3 infection.