Striebel James F, Race Brent, Carroll James A, Phillips Katie, Chesebro Bruce
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
J Gen Virol. 2016 Jun;97(6):1481-1487. doi: 10.1099/jgv.0.000442. Epub 2016 Mar 2.
Microglial activation is a hallmark of the neuroimmunological response to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion disease. The CX3C chemokine axis consists of fractalkine (CX3CL1) and its receptor (CX3CR1); these are expressed by neurons and microglia respectively, and are known to modulate microglial activation. In prion-infected mice, both Cx3cr1 and Cx3cl1 are altered, suggesting a role in disease. To investigate the influence of CX3C axis signalling on prion disease, we infected Cx3cr1 knockout (Cx3cr1-KO) and control mice with scrapie strains 22L and RML. Deletion of Cx3cr1 had no effect on development of clinical signs or disease incubation period. In addition, comparison of brain tissue from Cx3cr1-KO and control mice revealed no significant differences in cytokine levels, spongiosis, deposition of disease-associated prion protein or microglial activation. Thus, microglial activation during prion infection did not require CX3C axis signalling.
小胶质细胞激活是对阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和朊病毒病神经免疫反应的一个标志。CX3C趋化因子轴由趋化因子（CX3CL1）及其受体（CX3CR1）组成；它们分别由神经元和小胶质细胞表达，并且已知可调节小胶质细胞激活。在朊病毒感染的小鼠中，Cx3cr1和Cx3cl1均发生改变，提示其在疾病中起作用。为了研究CX3C轴信号传导对朊病毒病的影响，我们用羊瘙痒病毒株22L和RML感染了Cx3cr1基因敲除（Cx3cr1-KO）小鼠和对照小鼠。Cx3cr1的缺失对临床症状的发展或疾病潜伏期没有影响。此外，对Cx3cr1-KO小鼠和对照小鼠脑组织的比较显示，细胞因子水平、海绵状变性、疾病相关朊病毒蛋白的沉积或小胶质细胞激活方面没有显著差异。因此，朊病毒感染期间的小胶质细胞激活不需要CX3C轴信号传导。
