PCV2感染诱导的免疫抑制是猪圆环病毒病的主要特征。近年来研究认为巨噬细胞M2型极化与多种病毒诱导的免疫抑制密切相关。我们前期研究发现，PCV2感染可诱导巨噬细胞向M2型分化，敲除gC1qR可阻止PCV2诱导的M2型极化，提示gC1qR可能在PCV2诱导巨噬细胞M2型极化中发挥关键作用。本项目拟首先在PCV2感染猪和猪肺泡巨噬细胞后检测细胞活性、极化标志分子、相关信号通路活性和miRNA表达谱的变化，观察组织病变，明确PCV2感染后猪肺泡巨噬细胞极化状态的变化特征及其与组织病变的相关性，确定调控M2型极化的关键通路和miRNA；然后通过Cas9技术敲除gC1qR基因，检测gC1qR敲除对PCV2诱导的M2型极化、相关通路、miRNA以及组织病变的影响，明确gC1qR及其调控的信号通路和miRNA的作用，阐明PCV2诱导巨噬细胞M2型极化的分子机制，为认识PCV2的免疫抑制机制提供理论数据。

The immunosuppression caused by porcine circovirus type 2 (PCV2) infection is the major feature of PCV2-associated diseases. Recent studies have demonstrated that the M2 polarization of macrophages is associated with the immunosuppression caused by many viruses. Our previous studies have demonstrated that PCV2 infection could induce polarized M2 macrophages, whereas knockout of gC1qR gene could block the M2 polarization induced by PCV2, suggesting that gC1qR might play a pivotal role in the development of M2 polarization in PCV2-infected macrophages. However, it is still needed to further study the roles and regulatory mechanism of gC1qR in the M2 polarization of macrophage induced by PCV2. This project are firstly proposed to investigate that the changes of cell number, cell activity, polarized marker molecules, relative signaling pathways activities and miRNA expression profiles of porcine alveolar macrophages (PAMs), as well as the degree of tissue lesions, after PCV2 infect normal piglets or isolated primary PAMs, which will help us to determine the change pattern of polarized macrophage phonotype and correlation between polarization features of PCV2-infected macrophages and tissue lesions, and to identify the key signaling pathways and miRNAs that are involved in the regulation of M2 polarization induced by PCV2. Then, to develop gC1qR knockout porcine alveolar macrophages or piglet using CRISPR/cas9 genome editor tool, to investigate the changes of cell number, cell activity, polarized marker molecules, key signaling pathways activities, miRNA expression profiles, and to observe tissue lesions in either gC1qR knockout porcine alveolar macrophages or piglets, based on which to determine the roles and regulatory mechanism of gC1qR in the M2 polarization of macrophages induced by PCV2. The prospective results will help us to clarify the mechanisms of the macrophage M2 polarization during PCV2 infection , and provide a new insight into understanding the mechanism of PCV2 infection induction of immunosuppression.