Human Gene Set: GSE32986_GMCSF_VS_GMCSF_AND_CURDLAN_HIGHDOSE_STIM_DC_DN


Standard name GSE32986_GMCSF_VS_GMCSF_AND_CURDLAN_HIGHDOSE_STIM_DC_DN
Systematic name M8624
Brief description Genes down-regulated in bone marrow-derived dendritic cells CSF2 [GeneID=1437] versus CSF2 [GeneID=1437] and high dose of 1,3-beta-D-oligoglucan [PubChem=11375554].
Full description or abstract A simultaneous engagement of different pathogen recognition receptors provides a tailor made adaptive immunity for an efficient defence against distinct pathogens. For example, cross talk of TLR and c-type lectin signalling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-?B. Here, we extend this principle to a strong synergism between the Dectin-1 agonist, curdlan, and an inflammatory growth factor, GM-CSF. Both together act in synergy in inducing a strong inflammatory signature which converts immature DCs to potent effector DCs. A variety of cytokines (IL-1?, IL-6, TNF-?, IL-2 and IL-12p70), costimulatory molecules (CD80, CD86, CD40 and CD70), chemokines (CxCl1, CxCl2, CxCl3, CCl12, CCl17) as well as receptors and molecules involved in fugal recognition and immunity such as Mincle, Dectin-1, Dectin-2 and Pentraxin 3 are strongly up-regulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IKB? phosphorylation, in its rapid degradation and in enhanced nuclear translocation of all NF-?B subunits. We further identified MAPK ERK, as one possible integration site of both signals, since its phosphorylation was clearly augmented when curdlan was co-applied with GM-CSF. Our data demonstrate that the immunomodulatory activity of curdlan requires an additional signal provided by GM-CSF to successfully initiate a robust ?-glucan specific cytokine and chemokine response. The integration of both signals clearly prime and tailor a more effective innate and adaptive response against invading microbes and fungi.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22250091   Authors: Min L,Isa SA,Fam WN,Sze SK,Beretta O,Mortellaro A,Ruedl C
Exact source GSE32986_3112_200_DN
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Source species Mus musculus
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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