Surgery Department and Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Cell Immunol. 2010;262(2):96-104. doi: 10.1016/j.cellimm.2010.03.002. Epub 2010 Mar 6.
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.
丙型肝炎病毒（HCV）感染是一个主要的公共卫生问题，全球约有 3%的人口感染，给社会、经济和健康带来负担。在急性感染期间，不到 20%的感染者清除病毒，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干扰素-α（IFN-α）联合利巴韦林。尽管这种治疗方案的成本和副作用很高，但许多患者仍无法接受这种治疗，导致持续性 HCV 感染，进而发展为肝硬化和肝细胞癌。尽管尚未完全了解未能清除 HCV 感染的机制，但患者无法产生有效的抗 HCV 免疫是一个潜在的原因。我们假设，抗病毒免疫功能障碍是由于免疫抑制细胞的出现，同时伴随着刺激树突状细胞（DCs）和自然杀伤（NK）细胞的减少。我们进一步假设，应用能够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 的缓解。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，以阻断调节性细胞的抑制作用，并恢复 DCs 和 NK 细胞的刺激作用。
