Myocarditis, microbes and autoimmunity

Acute and chronic myocarditis can be caused by a number of infectious agents, including viruses, bacteria and protozoa. These diseases are refractory to treatment, and the development of rational therapies will require a detailed understanding of the mechanisms that underlie the pathological inflammatory responses. Here, we review three infectious myocarditides that, despite the dissimilarity of the microorganisms, share several common features: (i) the microbes replicate in the heart; but (ii) are difficult to isolate, in infectious form, during chronic disease; (iii) autoreactive antibodies and T cells specific for cardiac antigens have been identified in infected animals; and (iv) these autoreactive responses have been proposed as the main effectors of cell death, and myocardial damage. We critically evaluate the data, and we suggest that the findings can be reconciled without invoking autoimmunity as an effector mechanism. Alternative hypotheses to explain the tissue destruction are proposed.