STANDARD_NAME	GSE43700_UNTREATED_VS_IL10_TREATED_PBMC_DN
SYSTEMATIC_NAME	M9623
COLLECTION	C7:IMMUNESIGDB
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE43700_UNTREATED_VS_IL10_TREATED_PBMC_DN
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes down-regulated in peripheral blood monocytes (PBMC): control versus IL10 [GeneID=3586].
DESCRIPTION_FULL	The immune mechanisms that control resistance vs. susceptibility to mycobacterial infection in humans were investigated by studying leprosy skin lesions, the site where the battle between the host and the pathogen is joined. Using an integrative genomics approach, we found an inverse correlation between of IFN-beta and IFN-gamma gene expression programs at the site of disease. The Type II IFN, IFN-gamma and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in the lesions from patients with the self-healing tuberculoid form of the disease and mediated antimicrobial activity against the pathogen, Mycobacterium leprae in vitro. In contrast, the Type I IFN, IFN-beta and its downstream genes, including IL-27 and IL-10, were induced in monocytes by M. leprae in vitro, and were preferentially expressed in the lesions of disseminated and progressive lepromatous form. The IFN-gamma induced macrophage antimicrobial response was inhibited by IFN-beta/IL-10, by a mechanism involving blocking the generation of bioactive 1,25-dihyroxy vitamin D as well as inhibiting induction of antimicrobial peptides cathelicidin and DEFB4. The ability of IFN-B to inhibit the IFN-gamma induced vitamin D pathway including antimicrobial activity was reversed by neutralization of IL-10, suggesting a possible target for therapeutic intervention. Finally, a common IFN-beta and IL-10 gene signature was identified in both the skin lesions of leprosy patients and in the peripheral blood of active tuberculosis patients. Together these data suggest that the ability of IFN-beta to downregulate protective IFN-gamma responses provides one general mechanism by which some bacterial pathogens of humans evade protective host responses and contribute to pathogenesis.
PMID	23449998
GEOID	GSE43700
AUTHORS	Teles RM,Graeber TG,Krutzik SR,Montoya D,Schenk M,Lee DJ,Komisopoulou E,Kelly-Scumpia K,Chun R,Iyer SS,Sarno EN,Rea TH,Hewison M,Adams JS,Popper SJ,Relman DA,Stenger S,Bloom BR,Cheng G,Modlin RL
CONTRIBUTOR	Jernej Godec
CONTRIBUTOR_ORG	Dana-Farber Cancer Institute
EXACT_SOURCE	GSE43700_3701_200_DN
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	ABHD8,ABI1,ACSM2A,ACTL6B,ADRBK1,AHR,AK1,AMBP,AP3S2,ARHGEF25,ARL10,ARL2,ARTN,ASGR1,ATP6V0B,B4GALT3,BFSP1,BTK,C18orf8,C19orf48,C5orf34,C6orf64,CAP1,CCL4,CCRN4L,CD36,CDC26,CDK5,CDKN2B,CDKN2D,CEBPD,CEP350,CH25H,CHUK,CISD1,COG1,COL10A1,COL5A1,COL6A2,COQ3,CPA3,CTNNB1,CXCL10,CXCL9,CYB5A,CYP2F1,DBNDD2,DCTN3,DCUN1D5,DDIT4,DEF8,DENND5A,DFFB,DIAPH1,DNAJC2,DR1,DTYMK,DUSP16,DUT,EEF1B2,EFNA1,EIF1AX,ENSA,ENTPD6,ENTPD7,EPAS1,ERF,ERRFI1,EZH1,FABP5,FABP9,FAM32A,FCGR2B,FGA,FRAT1,G0S2,GADD45A,GADD45G,GBP7,GGA2,GKAP1,GMPPB,GPCPD1,GPN3,GRIA4,GSS,GTF3C4,GTPBP2,HAND1,HDC,HES5,HIST1H3F,IFIT3,IL17D,IL6,IRF1,IRF8,ISCA2,KCNJ11,KRT32,LCK,LOC283116,LYPLA2,MAFF,MAL,MAP3K11,MAP3K8,MATN4,MCOLN2,MED27,METAP1,MID1IP1,MIDN,MIPOL1,MOGS,MRPS26,MT1E,MT2A,MYD88,NDUFA8,NDUFA9,NDUFS6,NDUFV2,NFIL3,NOC4L,NOTCH3,NR1D1,NTPCR,OPRL1,PAH,PARK7,PCBD2,PCNT,PDC,PEX19,PFKL,PHYH,PITX1,PLAT,PLSCR1,PLXNA1,POLD3,POLD4,PON3,PREPL,PROCR,PSMG2,PTGER4,PTTG1,RAB18,RAC3,RAN,RCAN1,RETSAT,RGL1,RIT1,RIT2,RORC,RPA2,RPS10,RSPO1,RUNX1T1,S100A13,SAR1A,SCN9A,SELP,SEMA6B,SFMBT2,SH2B3,SLBP,SLC1A4,SLC2A1,SLC35C2,SLC46A1,SNAP23,SNTA1,SNX12,SOCS3,SPHK1,SSX2IP,STAT5B,SYNGR1,SYT10,TADA1,TEAD1,TMEM70,TPI1,TRAPPC3,TSPO2,TSPY1,UBE2D2,UBE2F,VNN1,XDH,XRCC5,ZFAND5,ZNF326,ZNHIT3,ZP1,ZWINT
GENE_SYMBOLS	ABHD8,ABI1,ACSM2A,ACTL6B,GRK2,AHR,AK1,AMBP,AP3S2,ARHGEF25,ARL10,ARL2,ARTN,ASGR1,ATP6V0B,B4GALT3,BFSP1,BTK,RMC1,C19orf48P,C5orf34,SAYSD1,CAP1,CCL4,NOCT,CD36,CDC26,CDK5,CDKN2B,CDKN2D,CEBPD,CEP350,CH25H,CHUK,CISD1,COG1,COL10A1,COL5A1,COL6A2,COQ3,CPA3,CTNNB1,CXCL10,CXCL9,CYB5A,CYP2F1,DBNDD2,DCTN3,DCUN1D5,DDIT4,DEF8,DENND5A,DFFB,DIAPH1,DNAJC2,DR1,DTYMK,DUSP16,DUT,EEF1B2,EFNA1,EIF1AX,ENSA,ENTPD6,ENTPD7,EPAS1,ERF,ERRFI1,EZH1,FABP5,FABP9,FAM32A,FCGR2B,FGA,FRAT1,G0S2,GADD45A,GADD45G,GBP7,GGA2,GKAP1,GMPPB,GPCPD1,GPN3,GRIA4,GSS,GTF3C4,GTPBP2,HAND1,HDC,HES5,H3C7,IFIT3,IL17D,IL6,IRF1,IRF8,ISCA2,KCNJ11,KRT32,LCK,TRIM49B,LYPLA2,MAFF,MAL,MAP3K11,MAP3K8,MATN4,MCOLN2,MED27,METAP1,MID1IP1,MIDN,MIPOL1,MOGS,MRPS26,MT1E,MT2A,MYD88,NDUFA8,NDUFA9,NDUFS6,NDUFV2,NFIL3,NOC4L,NOTCH3,NR1D1,NTPCR,OPRL1,PAH,PARK7,PCBD2,PCNT,PDC,PEX19,PFKL,PHYH,PITX1,PLAT,PLSCR1,PLXNA1,POLD3,POLD4,PON3,PREPL,PROCR,PSMG2,PTGER4,PTTG1,RAB18,RAC3,RAN,RCAN1,RETSAT,RGL1,RIT1,RIT2,RORC,RPA2,RPS10,RSPO1,RUNX1T1,S100A13,SAR1A,SCN9A,SELP,SEMA6B,SFMBT2,SH2B3,SLBP,SLC1A4,SLC2A1,SLC35C2,SLC46A1,SNAP23,SNTA1,SNX12,SOCS3,SPHK1,SSX2IP,STAT5B,SYNGR1,SYT10,TADA1,TEAD1,TMEM70,TPI1,TRAPPC3,TSPO2,TSPY1,UBE2D2,UBE2F,VNN1,XDH,XRCC5,ZFAND5,ZNF326,ZNHIT3,ZP1,ZWINT
FOUNDER_NAMES