State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Protein Cell. 2012 Aug;3(8):590-601. doi: 10.1007/s13238-012-2059-9. Epub 2012 Aug 4.
In the last decade, substantial progress has been made in understanding the molecular mechanisms involved in the initial host responses to viral infections. Herpesviral infections can provoke an inflammatory cytokine response, however, the innate pathogen-sensing mechanisms that transduce the signal for this response are poorly understood. In recent years, it has become increasingly evident that the Toll-like receptors (TLRs), which are germline-encoded pattern recognition receptors (PRRs), function as potent sensors for infection. TLRs can induce the activation of the innate immunity by recruiting specific intracellular adaptor proteins to initiate signaling pathways, which then culminating in activation of the nuclear factor kappa B (NF-κB) and interferon-regulatory factors (IRFs) that control the transcription of genes encoding type I interferon (IFN I) and other inflammatory cytokines. Furthermore, activation of innate immunity is critical for mounting adaptive immune responses. In parallel, common mechanisms used by viruses to counteract TLR-mediated responses or to actively subvert these pathways that block recognition and signaling through TLRs for their own benefit are emerging. Recent findings have demonstrated that TLR2 plays a crucial role in initiating the inflammatory process, and surprisingly that the response TLR2 triggers might be overzealous in its attempt to counter the attack by the virus. In this review, we summarize and discuss the recent advances about the specific role of TLR2 in triggering inflammatory responses in herpesvirus infection and the consequences of the alarms raised in the host that they are assigned to protect.
在过去的十年中,人们在理解宿主对病毒感染的初始反应所涉及的分子机制方面取得了重大进展。疱疹病毒感染会引发炎症细胞因子反应,然而,将这种反应信号转导的先天病原体感应机制还了解甚少。近年来,越来越明显的是,Toll 样受体(TLRs)作为先天免疫的模式识别受体(PRRs),是感染的有效传感器。TLRs 通过招募特定的细胞内衔接蛋白来启动信号通路,从而激活先天免疫,最终导致核因子 kappa B(NF-κB)和干扰素调节因子(IRFs)的激活,这些因子控制编码 I 型干扰素(IFN I)和其他炎症细胞因子的基因的转录。此外,先天免疫的激活对于启动适应性免疫反应至关重要。与此同时,病毒用来对抗 TLR 介导的反应或积极颠覆这些途径的共同机制也在出现,这些途径阻止了 TLR 对病毒的识别和信号传递。最近的发现表明,TLR2 在启动炎症过程中起着至关重要的作用,令人惊讶的是,TLR2 触发的反应可能过于热心,试图抵御病毒的攻击。在这篇综述中,我们总结和讨论了 TLR2 在触发疱疹病毒感染中的炎症反应中的具体作用,以及它们被分配来保护宿主的警报被触发的后果。