Turrin Nicolas P, Plante Marie-Michèle, Lessard Martine, Rivest Serge
Centre Hospitalier de l'Université Laval Research Center, Laboratory of Molecular Endocrinology, Department of Anatomy and Physiology, Laval University, 2705 Laurier Boulevard, Quebec City, Quebec, Canada.
Stem Cells. 2007 Dec;25(12):3165-72. doi: 10.1634/stemcells.2007-0508. Epub 2007 Aug 30.
Microglia and invading macrophages play key roles in the brain immune response. The contributions of these two populations of cells in health and diseases have yet to be clearly established. The use of chimeric mice receiving bone marrow-derived stem cell grafts from green fluorescent protein (GFP)-expressing mice has provided an invaluable tool to distinguish between local and blood-derived monocytic populations. The validity of the method is questioned because of the possible immune alterations caused by the irradiation of the recipient mouse. In this experiment, we compared the brain expression of innate immune markers Toll-like receptor 2, interleukin-1 beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in C57BL/6, GFP, and chimeric mice following an intracerebral injection of lipopolysaccharide. The endotoxin caused a marked transcriptional activation of all these innate immune genes in microglial cells across the ipsilateral side of injection. The expression patterns and signal intensity were similar in the brains of the three groups of mice. Consequently, the chimera technique is appropriate to study the role of infiltrating and resident immune cells in the brain without having immune compromised hosts. Disclosure of potential conflicts of interest is found at the end of this article.
小胶质细胞和侵入性巨噬细胞在大脑免疫反应中发挥关键作用。这两类细胞在健康和疾病中的作用尚未明确。使用接受来自绿色荧光蛋白(GFP)表达小鼠的骨髓衍生干细胞移植的嵌合小鼠,为区分局部和血液来源的单核细胞群体提供了一个宝贵的工具。由于受体小鼠受到辐射可能导致免疫改变,该方法的有效性受到质疑。在本实验中,我们比较了在脑内注射脂多糖后,C57BL/6小鼠、GFP小鼠和嵌合小鼠中固有免疫标志物Toll样受体2、白细胞介素-1β、肿瘤坏死因子-α和单核细胞趋化蛋白-1在大脑中的表达。内毒素在注射同侧的小胶质细胞中引起了所有这些固有免疫基因的显著转录激活。三组小鼠大脑中的表达模式和信号强度相似。因此,嵌合体技术适用于在宿主没有免疫受损的情况下研究浸润性和驻留免疫细胞在大脑中的作用。潜在利益冲突的披露见本文末尾。