Innate immune receptor activation in viral myocarditis: pathophysiologic implications

Abstract

The spectrum of clinical manifestations of viral myocarditis is extensive, ranging from asymptomatic infection to fulminant myocarditis. Viral infection is a major cause of acute myocarditis, with parvovirus B19 and human herpes virus 6 reported as most often responsible for viral myocarditis. The characteristics of the viral agent, together with the host's genetic susceptibility and the variability of the innate immune system, appear to be the main cause of this broad clinical spectrum. In viral infections the host's innate immune system acts as the first line of defense to prevent viral invasion and replication through cellular receptors. In the present review we analyze current knowledge of the activation of Toll-like receptors (TLR). Understanding the exact mechanism by which viral agents activate these receptors may help improve therapeutic strategies for viral myocarditis. TLRs play a dual role in the pathogenesis of viral myocarditis. In some models, through the activation of TLR3, they lead to a reduction of disease by direct or indirect inhibition of viral invasion and replication, while in other models they are responsible for exacerbation of the inflammatory response to viral infection, via activation of TLRs 4, 7, and 8. TLR4 also appears to be involved in activation of the autoimmune response.