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The potential use of Toll-like receptor agonists to restore the dysfunctional immunity induced by hepatitis C virus.

机译:Toll样受体激动剂在恢复丙型肝炎病毒诱导的功能障碍免疫方面的潜在用途。

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Hepatitis C virus (HCV) infection is a major public health concern with approximately 3% of the world's population is infected, posing social, economical and health burden. Less than 20% of the infected individuals clear the virus during the acute infection, while the rest develop chronic infection. The treatment of choice for HCV infection is pegylated interferon-alpha (IFN-alpha) in combination with ribavarin. Despite the cost and side effects of this treatment regimen, many patients fail this therapy and develop persistent HCV infection, leading to cirrhosis and hepatocellular carcinoma. Although the mechanisms underlying the failure to resolve HCV infection are poorly understood, the incapability of patients to develop effective anti-HCV immunity is a potential cause. We hypothesize that the dysfunctional anti-HCV immunity is due to the emergence of immunosuppressive cells coinciding with a decrease in the stimulatory dendritic cells (DCs) and natural killer (NK) cells. We further hypothesize that applying agents that can correct the imbalance between the immunosuppressive cells and stimulatory cells can results in resolution of chronic HCV. In this review article, we will discuss potential approaches, focusing on the use of Toll-like receptor agonists, to block the suppressive effects of the regulatory cells and restore the stimulatory effects of DCs and NK cells.
机译:丙型肝炎病毒(HCV)感染是主要的公共卫生问题,全球约3%的人口受到感染,给社会,经济和健康带来负担。在急性感染期间,只有不到20%的感染者清除了病毒,而其余的则发展为慢性感染。 HCV感染的治疗选择是聚乙二醇化干扰素-α(IFN-α)与利巴韦林联用。尽管该治疗方案具有成本和副作用,但许多患者仍无法使该治疗失败并发展为持续性HCV感染,从而导致肝硬化和肝细胞癌。尽管对解决HCV感染失败的潜在机制了解甚少,但患者无法发展有效的抗HCV免疫能力是潜在的原因。我们假设抗HCV免疫功能异常是由于免疫抑制细胞的出现与刺激性树突状细胞(DCs)和自然杀伤(NK)细胞的减少相吻合。我们进一步假设,可以纠正免疫抑制细胞和刺激细胞之间失衡的药物可以导致慢性HCV的消退。在这篇综述文章中,我们将讨论潜在的方法,重点是使用Toll样受体激动剂,以阻断调节细胞的抑制作用并恢复DC和NK细胞的刺激作用。

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