HIV/HCV共感染可引起临床上HCV IFN-α治疗应答率下降，天然免疫遭病毒破坏被认为是机制之一，但具体机制未明。我们前期研究发现浆细胞样树突状细胞（PDC）与自然杀伤（NK）细胞存在相互作用，IFN-α是其中的关键介导因子，同时发现HIV可显著损害PDC-NK细胞相互作用，HCV对其影响较小。本项目将研究共感染对PDC-NK细胞相互作用及PDC-NK抑制HCV复制的影响，同时研究IFN-ɑ在PDC-NK细胞系统中的作用以及共感染对IFN-ɑ介导作用的影响，还将采用RT-PCR阵列等技术确定共感染破坏PDC产生IFN-ɑ或NK细胞应答IFN-ɑ过程中的关键因子，为阐明共感染损害PDC-NK细胞相互作用的分子机制奠定基础。本项目期望为临床上HIV/HCV共感染者显著降低的HCV IFN-ɑ治疗应答率提供理论证据，为临床共感染治疗提供基于天然免疫的治疗新策略。

HIV/HCV co-infection is associated with a reduced rate of response to IFN-α based HCV therapy. Impairment of innate immunity by viruses is considered as one reason for this reduced response, but the details are still unclear. Our preliminary data showed that there is interaction between plasmacytoid dendritic cells (PDC) and natural killer (NK) cells, with IFN-α being the key player to mediate the PDC-NK interaction and direct NK activation. We also found that HIV dramatically impairs the PDC-NK interaction, whereas HCV has little effect on the interaction. This study will investigate the effects of HIV/HCV co-infection on PDC-NK interaction and inhibitory activity of PDC-NK cells on HCV replication. This study will also determine the essential role of IFN-α in PDC-NK interaction as well as the impact of co-infection on critical regulating function of IFN-α. On this basis, this study will use a series of biological techniques including RT- PCR array to screen IFN-α-related genes including the genes involved in IFN-α production in PDC and those related to IFN-α response in NK cells and identify the key factors responsible for the impairment caused by HIV/HCV co-infection. In summary, this study will reveal the impact of HIV/HCV co-infection on PDC-NK interaction and lay the foundation for clarifying the molecular mechanism(s) of impairment of PDC-NK interaction by co-infection. Our proposed study will provide evidence for the scientific understanding of the reduced response rate to IFN-α therapy among HIV/HCV co-infection population. it is of great clinical significance for the development of innate immunity-based new strategy against HIV/HCV infection.