Broad expression of Toll-like receptors in the human central nervous system.
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.
Bsibsi
Malika
M
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
Ravid
Rivka
R
Gveric
Djordje
D
van Noort
Johannes M
JM
D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002494:Central Nervous System Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D029721:Drosophila Proteins; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors