VRE感染是重症医学一大难题。蛋白类泛素化修饰Neddylation参与机体抗感染进程，但其在抗VRE感染中的作用仍不清楚。我们前期研究发现VRE感染小鼠的巨噬细胞CSN5表达降低，Neddylation蛋白增多，提示Neddylation参与巨噬细胞抗VRE感染进程。进一步研究发现，经Neddylation抑制剂(MLN4924)处理后，VRE感染小鼠巨噬细胞活性氧(ROS)减少、组织炎症加重、细菌负荷增多、小鼠生存率降低；体外干扰CSN5或MLN4924干预，分别增强或减弱巨噬细胞ROS的生成和杀菌能力。因此，我们推测CNS5可通过抑制Neddylation负向调控巨噬细胞抗VRE感染。本课题将利用巨噬细胞特异敲除Csn5小鼠，通过体内外实验，深入探讨CSN5对巨噬细胞抗VRE感染的影响及相关机制，从而揭示Neddylation抗VRE感染的新机制，为VRE感染的治疗提供新靶点。

Vancomycin resistant enterococci (VRE) infection is a major challenge in critical medicine. Neddylation, analogous to ubiquitination, is involved in the anti-infective process, but its role in anti-VRE infection remains unclear. Our preliminary experiments found that the expression of CSN5 in macrophages from VRE-infected mice was decreased, whereas the expression of neddylation protein was increased, suggesting that neddylation be involved in the process of macrophages against VRE infection. Further experiments showed that macrophages from VRE-infected mice treated with neddylation inhibitor (MLN4924) displayed a reduction in reactive oxygen species (ROS) production, an increase in tissue inflammation, an up-regulation of bacterial load, and a decline of survival rate; Interference with CSN5 siRNA or MLN4924 administration in vitro, respectively enhanced or attenuated ROS production and bactericidal ability of macrophages. Thus, we hypothesized that CNS5 could negatively regulate the role of macrophages against VRE infection via inhibiting neddylation. Using macrophage-specific Csn5 knockout mice, we will explore the effect of CSN5 on macrophage against VRE infection and the underlying mechanisms via a series of in vitro and in vivo experiments, attempting to reveal the new mechanisms of neddylation against VRE infection, and provide new targets to treat VRE infection.