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Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a shared set of signal transduction molecules, the biological effects of certain TLR agonists differ considerably. In macrophages and dendritic cells, stimulation by the prototypical stimuli CpG-DNA (TLR9), lipopolysaccharide (LPS; TLR4) and lipoteichoic acid (LTA; TLR2) resulted in striking differences in expression of IL-12. However, these stimuli induced similar amounts of the common proinflammatory cytokine TNFalpha. Surprisingly, an IL-12p40 promoter reporter construct was activated equally by CpG-DNA, LPS and LTA. Examinations of the chromatin structure of the endogenous IL-12p40 promoter revealed that nucleosome remodelling contributed to differential IL-12 induction. Upon stimulation, nucleosome architecture was changed to provide increased access to the IL-12p40 promoter. In dendritic cells, a differential induction of nucleosome remodelling at the IL-12p40 promoter was observed upon triggering with different TLR agonists. These results identify nucleosome remodelling as an additional restriction point in differential TLR signalling.

Original publication




Journal article


Embo rep

Publication Date





172 - 177


Animals, Cell Culture Techniques, Dendritic Cells, Genes, Reporter, Interleukin-12, Interleukin-12 Subunit p40, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Nucleosomes, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Protein Subunits, Receptors, Cell Surface, Signal Transduction, Teichoic Acids, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Transcription Factors