Abstract
TLR4 is a unique TLR because downstream signaling occurs via two separate pathways, as follows: MyD88 and Toll IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-beta (TRIF). In this study, we compared and contrasted the interplay of these pathways between murine dendritic cells (DCs) and macrophages during LPS stimulation. During TLR4 activation, neither pathway on its own was critical for up-regulation of costimulatory molecules in DCs, whereas the up-regulation of costimulatory molecules was largely TRIF dependent in macrophages. LPS-induced secreted factors, of which type I IFNs were one of the active components, played a larger role in promoting the up-regulation of costimulatory molecules in macrophages than DCs. In both cell types, MyD88 and TRIF pathways together accounted for the inflammatory response to LPS activation. Furthermore, signaling of both adaptors allowed maximal T cell priming by LPS-matured DCs, with MyD88 playing a larger role than TRIF. In sum, in our experimental systems, TRIF signaling plays a more important role in LPS-induced macrophage activation than in DC activation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptor Proteins, Vesicular Transport / deficiency
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Adaptor Proteins, Vesicular Transport / genetics
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Adaptor Proteins, Vesicular Transport / immunology*
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Animals
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Antigen-Presenting Cells / drug effects
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Antigen-Presenting Cells / immunology
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Bone Marrow / immunology
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Cell Differentiation / immunology*
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Cross-Priming / immunology
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Cytokines / biosynthesis
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Cytokines / immunology
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Dendritic Cells / cytology*
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology
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Mice
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Mice, Knockout
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Myeloid Differentiation Factor 88 / deficiency
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Myeloid Differentiation Factor 88 / genetics
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Myeloid Differentiation Factor 88 / immunology*
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Myeloid Differentiation Factor 88 / metabolism
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Signal Transduction / immunology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Toll-Like Receptor 4 / immunology*
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Up-Regulation
Substances
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Adaptor Proteins, Vesicular Transport
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Cytokines
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Lipopolysaccharides
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Myeloid Differentiation Factor 88
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TICAM-1 protein, mouse
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Tlr4 protein, mouse
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Toll-Like Receptor 4