Bsibsi Malika, Ravid Rivka, Gveric Djordje, van Noort Johannes M
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
J Neuropathol Exp Neurol. 2002 Nov;61(11):1013-21. doi: 10.1093/jnen/61.11.1013.
The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. In this study we investigated expression of TLRs in vitro by purified human microglia, astrocytes, and oligodendrocytes, and in vivo by immunohistochemical examination of brain and spinal cord sections. Cultured primary microglia were found to express mRNA encoding a wide range of different TLR family members while astrocytes and oligodendrocytes primarily express TLR2 and TLR3. Comparisons between microglia derived from a series of control subjects and neurodegenerative cases indicate distinct differences in levels of mRNA encoding the different TLRs indifferent microglia samples. Interestingly, expression of TLR proteins in cultured microglia as revealed by immunocytochemistry was restricted to intracellular vesicles, whereas in astrocytes they were exclusively localized on the cell surface. Finally, in vivo expression of TLR3 and TLR4 was examined by immunohistochemical analysis of brain and spinal cord sections from both control and multiple sclerosis brains, revealing enhanced expression of either TLR in inflamed CNS tissues. Together, our data reveal broad and regulated expression of TLRs both in vitro and in vivo by human glia cells.
Toll样受体（TLR）家族在控制对多种病原体相关分子的先天性免疫反应中起关键作用。在本研究中，我们通过纯化的人小胶质细胞、星形胶质细胞和少突胶质细胞在体外研究了TLR的表达，并通过对脑和脊髓切片进行免疫组织化学检查在体内进行了研究。发现培养的原代小胶质细胞表达编码多种不同TLR家族成员的mRNA，而星形胶质细胞和少突胶质细胞主要表达TLR2和TLR3。对一系列对照受试者和神经退行性疾病病例来源的小胶质细胞进行比较，结果表明不同小胶质细胞样本中编码不同TLR的mRNA水平存在明显差异。有趣的是，免疫细胞化学显示培养的小胶质细胞中TLR蛋白的表达局限于细胞内囊泡，而在星形胶质细胞中它们仅定位于细胞表面。最后，通过对对照和多发性硬化症脑的脑和脊髓切片进行免疫组织化学分析，检查了TLR3和TLR4在体内的表达，结果显示在炎症性中枢神经系统组织中这两种TLR的表达均增强。总之，我们的数据揭示了人神经胶质细胞在体外和体内TLR的广泛且受调控的表达。
