A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette-Guerin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

Dilated cardiomyopathy (DCM) is a potentially lethal disorder characterized by progressive impairment of cardiac function. Chronic myocarditis has long been hypothesized to be one of the causes of DCM. However, owing to the lack of suitable animal models of chronic myocarditis, its pathophysiology remains unclear. Here, we report a novel mouse model of chronic myocarditis induced by recombinant bacille Calmette-Guerin (rBCG) expressing a CD4(+) T-cell epitope of cardiac myosin heavy chain-alpha (rBCG-MyHC alpha). Mice immunized with rBCG-MyHC alpha developed chronic myocarditis, and echocardiography revealed dilation and impaired contraction of ventricles, similar to those observed in human DCM. In the heart, CD62L(-)CD4(+) T cells were increased and produced significant amounts of IFN-gamma and IL-17 in response to cardiac myosin. Adoptive transfer of CD62L(-)CD4(+) T cells induced myocarditis in the recipient mice, which indicated that CD62L(-)CD4(+) T cells were the effector cells in this model. rBCG-MyHC alpha-infected dendritic cells produced proinflammatory cytokines and induced MyHC alpha-specific T-cell proliferation and Th1 and Th17 polarization. This novel chronic myocarditis mouse model may allow the identification of the central pathophysiological and immunological processes involved in the progression to DCM.