**Part 2**

**Pathogenesis of Myocarditis** 

198 Myocarditis

Zhu WH, Han J, Nicosia RF. (2003). Requisite role of p38 MAPK in mural cell recruitment

Zhu WH, MacIntyre A, Nicosia RF. (2002). Regulation of angiogenesis by vascular

endothelial growth factor and angiopoietin-1 in the rat aorta model: distinct temporal patterns of intracellular signaling correlate with induction of angiogenic

during angiogenesis in the rat aorta model. *J Vasc Res* 40(2): 140-8.

sprouting. *Am J Pathol* 161(3): 823-30.

**10** 

*Germany* 

**Pattern-Recognition Receptors** 

*1Klinik für Kardiologie, Philipps-Universität Marburg and 2Klinik für Psychosomatische Medizin und Psychotherapie,* 

**Inflammatory Heart Disease** 

Volker Ruppert1 and Thomas Meyer2

 *Georg-August-Universität Göttingen,* 

**Sensing Viral Infection in Myocarditis and** 

Myocarditis is a potentially life-threatening heart disease affecting both children and adults which presents with a broad spectrum of clinical manifestations. Symptoms range from asymptomatic infection to a fulminant course that rapidly progresses to dilated cardiomyopathy (DCM) and heart failure. Viral infection of the heart is a major cause of acute myocarditis, leading to myocardial inflammation and tissue damage. Cellular infiltration in acute viral myocarditis may be caused by direct cytopathic effects of the virus, pathologic responses to persistent viral replication as well as autoimmunity triggered by the virus (Liu and Mason, 2001; Bowles and Vallejo, 2003; Linde et al., 2007; Rose et al., 2009; Rutschow et al., 2010). The cardiovirulence of the viral agent, together with the host´s genetic susceptibility and the variability in the innate and acquired immune system, appear to determine the extent of the inflammatory reaction, thereby predicting clinical outcome

Recently, meaningful advances have been made in our understanding of cellular mechanisms that are aimed to suppress viral propagation in inflammatory heart disease. In the first line of defense against viral replication, the host´s innate immune system is activated by unspecific, albeit effective interactions of cellular receptors with distinct pathogen-derived ligands. A variety of pattern-recognition receptors have been shown to be implicated in the detection of invading microbial agents (Kawai and Akira, 2010; Takeuchi and Akira, 2010). Upon viral infection of the heart, different signal pathways initiate an inflammatory response and orchestrate the concerted anti-viral defense machinery in a complex manner. Toll-like and RIG-I-like receptors are essential for the recognition of pathogen-associated molecular patterns and their activation induces intracellular signalling pathways which lead to the production of pro-inflammatory cytokines, chemokines, and interferons (Bowles and Vallejo, 2003; Fairweather et al., 2005; Triantafilou et al., 2005; Frantz et al., 2007; Linde et al., 2007; Yajima and Knowlton, 2009; Kawai and Akira, 2010; Takeuchi and Akira, 2010; Yamamoto and Takeda, 2010; Zhu and Mohan, 2010). Vice verse, interferons appear to induce the expression of a subset of toll-like receptors (Khoo et al., 2011). Type I interferons execute anti-viral responses by modulating cell growth,

**1. Introduction** 

(Kindermann et al., 2008).
