Sawhney Rohit, Visvanathan Kumar
Innate Immunity Laboratory, Department of Medicine, Monash University, Melbourne, Australia.
Antivir Ther. 2011;16(4):443-58. doi: 10.3851/IMP1820.
Toll-like receptors (TLRs) are an important part of the innate immune response to a variety of pathogens including hepatic viral infections. Activation of TLRs stimulates a complex intracellular signalling cascade that results in production of proinflammatory cytokines and interferons important for antiviral responses as well as induction of the adaptive arm of the immune system. There is substantial evidence for an important role for TLRs and TLR-mediated signalling in the pathogenesis and outcomes of hepatitis B and C in particular, but it might also influence responses to other viral hepatitis infections. Several single nucleotide polymorphisms (SNPs) of TLRs, relevant adaptor molecules and cytokines mediated by TLR signalling have been described that alter innate immune responses and have been implicated in a variety of human diseases including viral and other infections. There is now significant evidence that a number of TLR SNPs can affect various clinical outcomes in Caucasian patients with chronic HCV. However, the role of these polymorphisms in acute and other chronic hepatitis infections, including HBV as well as in non-Caucasian populations, has not been elucidated. In addition, results for SNPs downstream of TLR activation, such as in relevant cytokines, are inconsistent and their influence requires further investigation to determine the clinical significance of genetic variations in these mediators.
Toll样受体（TLRs）是机体对包括肝脏病毒感染在内的多种病原体进行固有免疫应答的重要组成部分。TLRs的激活会刺激复杂的细胞内信号级联反应，导致促炎细胞因子和干扰素的产生，这些对于抗病毒反应以及免疫系统适应性分支的诱导都很重要。有大量证据表明，TLRs及其介导的信号传导在乙型和丙型肝炎的发病机制及转归中起着重要作用，特别是在丙型肝炎中，但它也可能影响对其他病毒性肝炎感染的反应。已经描述了TLRs、相关衔接分子以及由TLR信号传导介导的细胞因子的几种单核苷酸多态性（SNP），这些多态性改变了固有免疫反应，并与包括病毒感染和其他感染在内的多种人类疾病有关。现在有大量证据表明，一些TLR SNP可以影响白种人慢性丙型肝炎患者的各种临床结局。然而，这些多态性在急性和其他慢性肝炎感染（包括乙型肝炎）以及非白种人群中的作用尚未阐明。此外，TLR激活下游SNP（如相关细胞因子中的SNP）产生的结果并不一致，其影响需要进一步研究以确定这些介质中基因变异的临床意义。
