Human Gene Set: GSE22935_UNSTIM_VS_12H_MBOVIS_BCG_STIM_MYD88_KO_MACROPHAGE_DN


Standard name GSE22935_UNSTIM_VS_12H_MBOVIS_BCG_STIM_MYD88_KO_MACROPHAGE_DN
Systematic name M7780
Brief description Genes down-regulated macrophages with MYD88 [GeneID=4615] knockout: untreated versus 12h after M. bovis BCG infection.
Full description or abstract Nitric oxide (NO) produced by macrophages (MØs) is toxic to both host tissues and invading pathogens and its regulation is therefore essential to suppress host cytotoxicity. MØ arginase 1 (Arg1) inhibits NO production by competing with NO synthases for arginine, the common substrate of NO synthases and arginases. Two signal transduction pathways control Arg1 expression in MØs. First, a MyD88-dependent pathway induces Arg1 in intracellular infections, while a second Stat6-dependent pathway is required for Arg1 expression in alternativelyactivated MØs. We found that mycobacteria-infected MØs produce soluble factors that induce Arg1 in an autocrine-paracrine manner via Stat3. We identify these factors as IL-6, IL-10 and GCSF. We further establish that Arg1 expression is controlled by the MyD88-dependent production of IL-6, IL-10 and G-CSF rather than cell intrinsic MyD88 signaling to Arg1. Our data reveal the MyD88-dependent pathway of Arg1induction following BCG infection requires Stat3 activation and may result in the development of an immunosuppressive niche in granulomas due to the induced Arg1 production in surrounding uninfected MØs
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 20716764   Authors: Qualls JE,Neale G,Smith AM,Koo MS,DeFreitas AA,Zhang H,Kaplan G,Watowich SS,Murray PJ
Exact source GSE22935_2878_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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