title: Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury.
abstract: 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.
authors.affiliation: Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Hordur S
authors.initials: HS
authors.lastname: Hardarson
authors.forename: J Scott
authors.initials: JS
authors.lastname: Baker
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.forename: Enkhsaikhan
authors.initials: E
authors.lastname: Purevjav
authors.forename: Chien-Hua
authors.initials: CH
authors.lastname: Huang
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bowles
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Vallejo
mesh_terms: D000818:Animals; D018188:Cardiovirus Infections / Q000276:immunology* / Q000821:virology; D004686:Encephalomyocarditis virus; D018869:Heat-Shock Response / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000276:immunology*
chemical_list: D051196:Toll-Like Receptor 3