Broad expression of Toll-like receptors in the human central nervous system
Broad expression of Toll-like receptors in the human central nervous system
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DOI：
10.1093/jnen/61.11.1013
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发表时间：
2002-11-01
影响因子：
3.2
通讯作者：
van Noort, JM
中科院分区：
文献类型：
--
作者：
Bsibsi, M;Ravid, R;van Noort, JM
Toll样受体（TLR）家族在控制针对多种病原体相关分子的先天免疫应答中起关键作用。在这项研究中，我们研究了TLRs的表达在体外纯化的人小胶质细胞，星形胶质细胞和少突胶质细胞，并在体内的脑和脊髓切片的免疫组化检查。发现培养的原代小胶质细胞表达编码广泛的不同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TLR 2和TLR 3。来自一系列对照受试者和神经变性病例的小胶质细胞之间的比较表明，不同小胶质细胞样品中编码不同TLR的mRNA水平存在明显差异。有趣的是，TLR蛋白在培养的小胶质细胞中的表达所揭示的免疫细胞化学被限制在细胞内的囊泡，而在星形胶质细胞中，他们专门定位于细胞表面上。最后，通过对来自对照和多发性硬化脑的脑和脊髓切片的免疫组织化学分析来检查TLR3和TLR4的体内表达，揭示了TLR在发炎的CNS组织中的增强表达。总之，我们的数据揭示了广泛的和调节的TLR表达在体外和体内的人神经胶质细胞。
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 in different 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.