Abstract
Toll-like receptors (TLRs) mediate innate immune responses to microbes. TLR2, TLR5, TLR6, and TLR9 have been implicated in responses to bacterial components, and TLR4 is the receptor for Gram-negative bacteria. Recently, TLR4 was described to function in respiratory syncytial virus-induced NF-kappaB activation. Here we have analyzed TLR1-9 mRNA expression in human primary macrophages infected with influenza A and Sendai viruses. TLR1, TLR2, TLR4, TLR6, and TLR8 mRNAs were expressed at basal levels in macrophages. Viral infection enhanced TLR1, TLR2, TLR3, and TLR7 mRNA expression, and neutralizing anti-IFN-alpha/beta antibodies downregulated gene expression of these TLRs. Exogenously added IFN-alpha upregulated TLR1, TLR2, TLR3, and TLR7 mRNA expression in macrophages, as well as TLR3 mRNA expression in epithelial and endothelial cell lines. IFN-gamma enhanced the expression of TLR1 and TLR2 mRNA in macrophages, and TLR3 in epithelial and endothelial cells. The data suggests a novel role for IFNs in the activation of innate immunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies / immunology
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drosophila Proteins*
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Humans
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Influenza A virus / physiology*
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Interferons / antagonists & inhibitors
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Interferons / immunology
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Interferons / metabolism*
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Macrophages / metabolism*
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Macrophages / virology*
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Membrane Glycoproteins / genetics*
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Neutralization Tests
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Cell Surface / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Sendai virus / physiology*
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Toll-Like Receptor 1
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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 Receptor 5
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Toll-Like Receptor 7
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Toll-Like Receptor 8
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Toll-Like Receptor 9
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Toll-Like Receptors
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Up-Regulation*
Substances
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Antibodies
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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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TLR5 protein, human
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TLR7 protein, human
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TLR8 protein, human
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TLR9 protein, human
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Toll-Like Receptor 1
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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 Receptor 5
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Toll-Like Receptor 7
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Toll-Like Receptor 8
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Toll-Like Receptor 9
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Toll-Like Receptors
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Interferons