**6. References**


Innate immunity is the rapid host response and occurs within hours of microbial infections. Although a major role for innate immunity is to help dampen microbe replication until the adaptive immune response is adequately developed for final microbial elimination, another major role for innate immunity is to control and direct the developing adaptive immune response. There is substantial cross-talk between innate lymphocyte effectors during myocarditis. Both NKT and a population of γδ cells recognize CD1d, a non-classical MHC class I-like molecule. However, evidence implies that while NKT cells are protective in myocarditis, γδ cells are pro-inflammatory and pathogenic. Interesting similarities have been found in the role of NKT and γδ cells in two different myocarditis mouse models: CVB3 and Trypanosoma cruzi induced myocarditis. The fact that similar immune processes of pathogenicity and protection appear to function in these two models provides circumstantial evidence that these innate effectors may have identical roles in other forms of myocarditis and also in clinical disease. To date, little evidence actually exists for innate effectors in clinical disease. However, the strong association between microbial infections

and myocarditis in humans means that innate immunity should be important.

This work was supported by HL108371 from the National Institutes of Health.

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**1. Introduction** 

al. 2008).

**12** 

*Canada* 

**The Key Players of** 

*University of British Columbia* 

**Coxsackievirus-Induced Myocarditis** 

Myocarditis is a devastating cardiac disease causing death in children and young adults worldwide (Esfandiarei et al. 2008). The disease is clinically characterized by inflammation of the myocardium and degeneration of myocytes. Clinical symptoms of viral myocarditis range from flu-like and/or gastrointestinal illness to ventricular dysfunction ending commonly in heart failure. Acute disease is accompanied by multiorgan abnormalities and presents mostly in neonates and young children. Chronic disease occurs in one third of patients and is likely a consequence of autoimmune-mediated myocardial injury and viral persistence. As cardiac myocytes are destroyed by virus and/or self-induced cytopathic immune effects, excessive repair or fibrosis of myocardial tissue impairs disease progression rather than protects the tissue from further damage. Fibrosis or scar tissue, can lead to abnormal ventricular architecture that inevitably leads to the disruption of its function. At this stage of disease, chronic myocarditis progresses to dilated cardiomyopathy and can eventually lead to congestive heart failure (Esfandiarei et

The exact cause for myocarditis is still unknown though pathogen infections, hypersensitivity reactions, and systemic and autoimmune diseases are all likely contributing factors. It is suggested that acute viral myocarditis that progresses to chronic disease mirrors the clinical pathology observed with dilated cardiomyopathy patients and is likely the result of an inappropriate immune response after virus infection that leads to chronic

Tracking the incidence of myocarditis is challenging. It is difficult to determine the potential disease burden to populations since there is a range in clinical symptoms associated with disease and endomyocardial biopsy to diagnose disease is rarely practised (Blauwet et al. 2010). Though mounting evidence of viral genomes recovered from chronic dilated cardiomyopathy patients provides some insight in to the potential burden of this devastating cardiac disease (Kuhl et al. 2005). Viral-induced myocarditis and dilated cardiomyopathy leads to a worse prognosis than other possible myocarditis/dilated cardiomyopathy etiological agents. Isolation of enteroviral RNA from endocardial biopsies of myocarditis and dilated cardiomyopathy patients renders these patients six times more susceptible to death after two years from diagnosis compared to virus-negative patients (Why et al. 1994). Sex is another contributing factor to disease susceptibility. Initially, it was

inflammation and virus persistence (Escher et al. 2011).

Pamela J. Lincez, Marine Walic and Marc S. Horwitz

*Department of Microbiology and Immunology,* 

