Innate immune activation in experimental autoimmune myocarditis

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and frequently
results from postinfectious autoimmunity. Its pathophysiology is modeled by
experimental autoimmune myocarditis (EAM), a CD4+ T-cell mediated murine
model of postinfectious heart disease. My thesis focuses on the role of innate
mechanisms in inflammatory heart disease using the EAM model. In this context
we specifically addressed the role of the Toll-like Receptor (TLR) signalling
adaptor molecule MyD88 and the Interferon-alpha-beta Receptor (IFNαβR).
First, we addressed the role of MyD88 in EAM induction. In contrast to wild-type
(wt) control littermates, MyD88 deficient mice were protected from EAM after
immunization with alpha-myosin heavy chain derived peptide (MyHC-alpha) and
complete Freund`s adjuvant (CFA). Disease resistance of MyD88 deficient mice
resulted from impaired expansion of heart-specific CD4+ T-cells after
immunization. We further showed that MyD88 deficient primary antigen
presenting dendritic cells were defective in their capacity to prime CD4+ T-cells.
This defect mainly resulted from the inability of MyD88 deficient DCs to release
TNF-alpha. However, repetitive injection of activated, MyHC-