Human Gene Set: GSE9946_IMMATURE_VS_MATURE_STIMULATORY_DC_UP


Standard name GSE9946_IMMATURE_VS_MATURE_STIMULATORY_DC_UP
Systematic name M415
Brief description Genes up-regulated in dendritic cells: immature versus mature stimulatory.
Full description or abstract Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype. In summary, regulatory myeloid DC and macrophages may play a dual role during life-threatening granulomatous infections, such as tuberculosis: on one hand, regulatory myeloid cells promote pathogen containment by efficiently killing intracellular bacteria, on the other hand these cells inhibit granuloma-associated T cells and thereby might be involved in the retention of TNF-controlled granuloma integrity protecting the host from granuloma break-down and pathogen dissemination.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 18802101   Authors: Popov A,Driesen J,Abdullah Z,Wickenhauser C,Beyer M,Debey-Pascher S,Saric T,Kummer S,Takikawa O,Domann E,Chakraborty T,Krönke M,Utermöhlen O,Schultze JL
Exact source GSE9946_2753_200_UP
Related gene sets (show 11 additional gene sets from the source publication)

(show 4 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
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 137 genes
Gene families ? Categorize these 137 genes by gene family
Show members (show 200 source identifiers mapped to 137 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.