HCV急性感染后除少数个体发生病毒自发清除外，多数进展为慢性感染。感染早期宿主体内固有免疫应答能力强弱与临床转归密切关联。HCV慢性感染状态下多种固有免疫应答细胞如NK细胞、树突状细胞等均报道有一定程度的功能损伤，而对自发清除者体内固有免疫状态研究较少，尤其是对分泌IL-10、TNF-α等为特征的单核细胞功能缺乏深入探讨。本项目基于HCV自发清除者宿主固有免疫状态的独特性，聚焦于固有免疫应答主要效应细胞群之一的单核细胞，比较研究外周血单核细胞及其亚群在HCV慢性感染和自发清除者中免疫功能的变化规律和差异性，特别对单核细胞各亚群对TLR配体和干扰素（IFN）的反应特征、刺激T细胞增殖能力和PD1/PDL-1负调控信号参与单核细胞活化的作用机制等进行综合分析，旨在挖掘在HCV病毒自发清除者外周血单核细胞免疫效应的功能特点和潜在机制，为探索单核细胞相关的免疫控制新策略寻找靶点。

Development of HCV infection is typically followed by chronic hepatitis C in most patients, while spontaneous HCV viral clearance occurs in only a minority of subjects. It is demonstrated that status of host innate immunity in early stage of HCV infection is closely associated with clinical outcome. Although functional impairments of some innate immune cells, such as NK cells and dentritic cells were identified in HCV long-term persistence, the status of innate immunity in spontaneous HCV recovered subjects was rarely investigated, especially of monocyte which is characterized by secretion of IL-10, TNF-α and other cytokines. Based on the unique nature of innate immunity in HCV recovered subjects, this study will focuse on characteristics of monocytes and diferences of immune response mediated by monocyte and its subsets in HCV chronic infected patients and HCV spontaneous recovered individuals. Comprehensive analysis of immune response mediated by monocyte and its subsets upon TLR ligands and interferon stimulation, the effects of monocyte-mediated T cell proliferation, and PD1/PDL-1 negative regulatory signals involved in monocyte activation will be studied in this proposal. This study will explore the functional characteristics and potential mechanisms of monocyte-mediated immunity in HCV infected patients and look for novel targets based on monocyte associated immune control strategy.