Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury
Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury
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DOI：
10.1152/ajpheart.00398.2006
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Vallejo, Jesus G.
中科院分区：
文献类型：
--
作者：
Hardarson, Hordur S.;Baker, J. Scott;Vallejo, Jesus G.
肠道病毒引起的心肌损伤可导致严重的心力衰竭。到目前为止，对心脏中有助于宿主防御的早期先天应激反应知之甚少。Toll样受体3(TLR3)在先天抗病毒反应的启动中起重要作用。我们研究了识别病毒双链RNA的TLR3在脑心肌炎病毒(EMCV)感染中的作用。为了检测TLR3对EMCV感染的保护作用，我们用50个空斑形成单位的EMCV感染了TLR3缺陷小鼠。与TLR3(-/-)小鼠相比，TLR3缺陷(TLR3(-/-))小鼠更容易受到EMCV感染，心脏中的病毒载量明显较高。组织病理学检查显示，TLR3(-/-)组小鼠心肌炎性改变明显轻于TLR3(-/-)组。TLR3(-/-)小鼠感染EMCV后，心脏促炎细胞因子和趋化因子表达受损。然而，在感染EMCV的TLR3(-/-)小鼠中，干扰素-β的表达并未受到损害。EMCV感染导致依赖TLR3的先天应激反应，参与介导对病毒诱导的心肌损伤的保护作用。
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.