Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury

Enterovirus-induced myocardial injury can lead to severe heart failure. To date, little is known about the early innate stress response that contributes to host defense in the heart. Toll-like receptor 3 ( TLR3) is important in the initiation of the innate antiviral response. We investigated the involvement of TLR3, which recognizes viral double- stranded RNA, on encephalomyocarditis virus ( EMCV) infection. To examine the contribution of TLR3 in protection from EMCV infection, we infected mice deficient in TLR3 with 50 plaque-forming units of EMCV. TLR3-deficient ( TLR3 (-/-)) mice were more susceptible to EMCV infection and had a significantly higher viral load in the heart compared with TLR3 (-/-) mice. Histopathological examination showed that the inflammatory changes of the myocardium were less marked in TLR3(-/-) than in TLR3(-/-) mice. TLR3(-/-) mice had impaired proinflammatory cytokine and chemokine expression in the heart following EMCV infection. However, the expression of interferon-beta was not impaired in EMCV- infected TLR3(-/-) mice. EMCV infection leads to a TLR3- dependent innate stress response, which is involved in mediating protection against virus- induced myocardial injury.