Human Gene Set: GSE36078_WT_VS_IL1R_KO_LUNG_DC_UP


Standard name GSE36078_WT_VS_IL1R_KO_LUNG_DC_UP
Systematic name M9299
Brief description Genes up-regulated in Lung dendritic cell from untreated wildtype mice versus Lung dendritic cell from untreated IL-1R mice.
Full description or abstract Discrimination between self vs. non-self and adequate response to infection and tissue damage are fundamental functions of the immune system. The rapid and global spread of known and emerging viruses is a testament that the timely detection of viral pathogens that reproduce within host cells, presents a formidable challenge to the immune system. To gain access to a proper reproductive niche, many pathogens travel via the host vasculature and therefore become exposed to humoral factors of the innate immune system. Although a cascade of coagulation factors plays a fundamental role in host defense for ?living fossils? such as horseshoe crabs (Xiphosurida spp), the role of the coagulation system in activation of innate responses to pathogens in higher organisms remains unclear. When human type C adenovirus (HAdv) enters the circulation, 240 copies of coagulation factor X (FX) bind to the virus particle with picomolar affinity. Here, using molecular dynamics flexible fitting (MDFF) and high resolution cryo-electron microscopy (cryo-EM), we defined the interface between the HAdv5 hexon protein and FX at pseudo-atomic level. Based on this structural data, we introduced a single amino acid substitution, T424A, in the hexon that completely abrogated FX interaction with the virus. In vivo genome-wide transcriptional profiling revealed that FX-binding-ablated virus failed to activate a distinct network of the early response genes, whose expression depends on transcription factor NFKB1. Deconvolution of the signaling network responsible for early gene activation showed that the FX-HAdv complex triggers MyD88/TRIF/TRAF6 signaling upon activation of toll-like receptor 4 (TLR4) that serves as a principal sensor of FX-virus complex in vivo. Our study implicates host factor ?decoration? of the virus as a mechanism to trigger innate immune sensor that respond to a misplacement of coagulation FX from the blood into intracellular macrophage compartments upon virus entry into the cell. Our results further the mounting evidence of evolutionary conservation between the coagulation system and innate immunity.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 23019612   Authors: Doronin K,Flatt JW,Di Paolo NC,Khare R,Kalyuzhniy O,Acchione M,Sumida JP,Ohto U,Shimizu T,Akashi-Takamura S,Miyake K,MacDonald JW,Bammler TK,Beyer RP,Farin FM,Stewart PL,Shayakhmetov DM
Exact source GSE36078_3659_200_UP
Related gene sets (show 13 additional gene sets from the source publication)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform or
identifier namespace		 HUMAN_GENE_SYMBOL
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 200 genes
Gene families ? Categorize these 200 genes by gene family
Show members (show 200 source identifiers mapped to 200 genes)
Version history 7.3: Moved to ImmuneSigDB sub-collection.

See MSigDB license terms here. Please note that certain gene sets have special access terms.