MyD88 Signaling Controls Autoimmune Myocarditis Induction

Background— Experimental autoimmune myocarditis (EAM) is a CD4+ T-cell–mediated mouse model of postviral cardiomyopathy. Activation of interleukin-1 type 1 and Toll-like receptors that share the common downstream adaptor molecule MyD88 is required for disease induction. The specific role of MyD88 in myocarditis, however, is not known. Methods and Results— In contrast to control littermates, MyD88−/− mice were protected from myocarditis after immunization with α-myosin heavy chain–derived peptide (MyHC-α) and complete Freund’s adjuvant. Disease resistance of MyD88−/− mice resulted from impaired expansion of heart-specific CD4+ T cells after immunization. Intrinsic defects of MyD88−/− CD4+ T cells were excluded. In contrast, MyD88−/− but not MyD88+/+ primary antigen presenting dendritic cells (DCs) were defective in their capacity to prime CD4+ T cells. This defect mainly resulted from the inability of MyD88−/− DCs to release tumor necrosis factor-α. The critical role of MyD88 signaling in DCs in the periph...