Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Astrocytes / immunology
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Astrocytes / metabolism
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Astrocytes / pathology
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Cells, Cultured
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Central Nervous System / immunology*
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Central Nervous System / metabolism
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Central Nervous System / pathology
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Central Nervous System Infections / immunology*
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Central Nervous System Infections / metabolism
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Central Nervous System Infections / pathology
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Drosophila Proteins*
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Encephalitis / immunology*
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Encephalitis / metabolism
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Encephalitis / pathology
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Female
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Gene Expression Regulation / immunology
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Humans
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Immune System / immunology*
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Immune System / metabolism
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Immunohistochemistry
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Male
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism*
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Microglia / immunology
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Microglia / metabolism
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Middle Aged
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Multiple Sclerosis / immunology
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Multiple Sclerosis / metabolism
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Multiple Sclerosis / pathology
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Neuroglia / immunology*
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Neuroglia / metabolism
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Oligodendroglia / immunology
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Oligodendroglia / metabolism
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Oligodendroglia / pathology
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RNA, Messenger / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / metabolism*
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Toll-Like Receptor 2
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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Drosophila Proteins
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Cell Surface
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TLR2 protein, human
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TLR3 protein, human
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TLR4 protein, human
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Toll-Like Receptor 2
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors