Role of DC-NK cross-talk in viral infection: defining the critical molecular mechanisms

树突状细胞（DC）是参与激活免疫系统以响应感染的高度特化的细胞亚群。树突状细胞可以激活T细胞，然后摧毁感染或受损的细胞。最近的证据表明，自然杀伤（NK）细胞的激活也可能是树突状细胞的一个重要功能。NK细胞专门用于去除受损细胞，并且已被证明在控制病毒感染以及肿瘤生长和扩散方面特别重要。这项工作的主要目的是确定树突状细胞在病毒感染期间激活NK细胞的机制。将使用充分表征的鼠巨细胞病毒模型（MCMV）来解决该问题。MCMV是人巨细胞病毒感染（HCMV）的模型。HCMV感染通常对健康个体没有风险，然而，在免疫抑制的人中，如癌症或艾滋病患者，HCMV是死亡的重要原因。MCMV感染模型提供了关于免疫系统如何控制感染以及病毒用于规避这些过程的机制的重要见解。拟议的研究将增强我们对树突状细胞如何调节自然杀伤细胞功能以及病毒如何干扰这一过程的理解。更重要的是，这些结果将为如何修改免疫治疗方案以提高有效性提供重要见解。

Dendritic cells (DC) are a highly specialized subset of cells involved in activating the immune system in response to infection. Dendritic cells can activate T cells, which then destroy infected or damaged cells. Recent evidence has suggested that activation of natural killer (NK) cells may also be an important function of dendritic cells. NK cells specialize in the removal of damaged cells and have been shown to be particularly important in controlling viral infection and tumour growth and spread. The central aim of this work is to determine what mechanisms are used by dendritic cells to activate NK cells during viral infection. The well characterized murine cytomegalovirus model (MCMV) will be used to address this question. MCMV is a model for human cytomegalovirus infection (HCMV). HCMV infection usually poses no risk to healthy individuals, however, in people who are immunosuppressed, such as cancer or AIDS patients, HCMV is a significant cause of mortality. The MCMV infection model has provided important insights as to how the immune system controls infection, and the mechanisms utilized by the virus to circumvent these processes. The proposed studies will enhance our understanding of how natural killer cell function is regulated by dendritic cells, and how viruses may interfere with this process. More importantly, the results will provide critical insights into how immunotherapy protocols may be modified to enhance effectiveness.