Human Gene Set: GSE2706_LPS_VS_R848_AND_LPS_8H_STIM_DC_DN


Standard name GSE2706_LPS_VS_R848_AND_LPS_8H_STIM_DC_DN
Systematic name M4728
Brief description Genes down-regulated in comparison of dendritic cells (DC) stimulated with LPS (TLR4 agonist) at 8 h versus DCs stimulated with LPS (TLR4 agonist) and R848 for 8 h.
Full description or abstract Toll like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). Since pathogens may contain several agonists we asked whether different TLRs may synergize in DC activation. We report that in human and mouse DC TLR3 or TLR4 potently synergize with TLR7, TLR8 or TLR9 in the induction of selected cytokine genes. Upon synergistic stimulation, IL-12, IL-23 and Delta-4 are induced at levels 50-100 fold higher than those induced by optimal concentrations of single agonists, leading to enhanced and sustained TH1 polarizing capacity. Using microarray analysis we show that only 1.5% of the transcripts induced by single TLR agonists are synergistically regulated by combinations of TLR4 and TLR8 agonists. These results identify a combinatorial code by which DCs discriminate pathogens and provide (suggest) a rationale to design adjuvants for TH1 responses. Series_overall_design: 3 untreated, 3 treated with LPS at 2h, 3 treated with LPS at 8h, 3 treated with R848 at 2h, 3 treated with R848 at 8h, 3 treated with LPS + R848 at 2h, 3 treated with LPS + R848 at 8h
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 15995707   Authors: Napolitani G,Rinaldi A,Bertoni F,Sallusto F,Lanzavecchia A
Exact source GSE2706_1848_200_DN
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Source species Homo sapiens
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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