KEGG   PATHWAY: hsa05152
Entry
hsa05152                    Pathway                                
Name
Tuberculosis - Homo sapiens (human)
Description
Tuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent infections, and about 10% of latent infections develop active diseases when their immune system is impaired due to the age, other diseases such as AIDS or exposure to immunosuppressive drugs. TB is transmitted through the air and primarily attacks the lungs, then it can spread by the circulatory system to other parts of body. Once TB bacilli have entered the host by the respiratory route and infected macrophages in the lungs, they interfere with phagosomal maturation, antigen presentation, apoptosis and host immune system to establish persistent or latent infection.
Class
Human Diseases; Infectious disease: bacterial
Pathway map
hsa05152  Tuberculosis
hsa05152

Disease
H00342  Tuberculosis
Organism
Homo sapiens (human) [GN:hsa]
Gene
7124  TNF; tumor necrosis factor [KO:K03156]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
8717  TRADD; TNFRSF1A associated via death domain [KO:K03171]
8772  FADD; Fas associated via death domain [KO:K02373]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
843  CASP10; caspase 10 [KO:K04400] [EC:3.4.22.63]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
637  BID; BH3 interacting domain death agonist [KO:K04726]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
54205  CYCS; cytochrome c, somatic [KO:K08738]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
815  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
3458  IFNG; interferon gamma [KO:K04687]
3459  IFNGR1; interferon gamma receptor 1 [KO:K05132]
3460  IFNGR2; interferon gamma receptor 2 [KO:K05133]
3716  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
3717  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
6772  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
4261  CIITA; class II major histocompatibility complex transactivator [KO:K08060] [EC:2.7.11.1]
5993  RFX5; regulatory factor X5 [KO:K08061]
8625  RFXANK; regulatory factor X associated ankyrin containing protein [KO:K08062]
5994  RFXAP; regulatory factor X associated protein [KO:K08063]
4800  NFYA; nuclear transcription factor Y subunit alpha [KO:K08064]
4801  NFYB; nuclear transcription factor Y subunit beta [KO:K08065]
4802  NFYC; nuclear transcription factor Y subunit gamma [KO:K08066]
1385  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
972  CD74; CD74 molecule [KO:K06505]
1387  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
3586  IL10; interleukin 10 [KO:K05443]
3587  IL10RA; interleukin 10 receptor subunit alpha [KO:K05134]
3588  IL10RB; interleukin 10 receptor subunit beta [KO:K05135]
1520  CTSS; cathepsin S [KO:K01368] [EC:3.4.22.27]
26253  CLEC4E; C-type lectin domain family 4 member E [KO:K10059]
2207  FCER1G; Fc epsilon receptor Ig [KO:K07983]
64581  CLEC7A; C-type lectin domain containing 7A [KO:K10074]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
6850  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
64170  CARD9; caspase recruitment domain family member 9 [KO:K12794]
10892  MALT1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
8915  BCL10; BCL10 immune signaling adaptor [KO:K07368]
64127  NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165]
8767  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
3313  HSPA9; heat shock protein family A (Hsp70) member 9 [KO:K04043]
3329  HSPD1; heat shock protein family D (Hsp60) member 1 [KO:K04077] [EC:5.6.1.7]
3929  LBP; lipopolysaccharide binding protein [KO:K05399]
7097  TLR2; toll like receptor 2 [KO:K10159]
7096  TLR1; toll like receptor 1 [KO:K05398]
10333  TLR6; toll like receptor 6 [KO:K10169]
7099  TLR4; toll like receptor 4 [KO:K10160]
929  CD14; CD14 molecule [KO:K04391]
114609  TIRAP; TIR domain containing adaptor protein [KO:K05403]
4615  MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729]
51135  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3654  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
3656  IRAK2; interleukin 1 receptor associated kinase 2 [KO:K04731] [EC:2.7.11.1]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
4843  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
3569  IL6; interleukin 6 [KO:K05405]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
3606  IL18; interleukin 18 [KO:K05482]
51561  IL23A; interleukin 23 subunit alpha [KO:K05426]
3552  IL1A; interleukin 1 alpha [KO:K04383]
3553  IL1B; interleukin 1 beta [KO:K04519]
1051  CEBPB; CCAAT enhancer binding protein beta [KO:K10048]
1054  CEBPG; CCAAT enhancer binding protein gamma [KO:K10049]
54106  TLR9; toll like receptor 9 [KO:K10161]
3439  IFNA1; interferon alpha 1 [KO:K05414]
3440  IFNA2; interferon alpha 2 [KO:K05414]
3441  IFNA4; interferon alpha 4 [KO:K05414]
3442  IFNA5; interferon alpha 5 [KO:K05414]
3443  IFNA6; interferon alpha 6 [KO:K05414]
3444  IFNA7; interferon alpha 7 [KO:K05414]
3445  IFNA8; interferon alpha 8 [KO:K05414]
3446  IFNA10; interferon alpha 10 [KO:K05414]
3447  IFNA13; interferon alpha 13 [KO:K05414]
3448  IFNA14; interferon alpha 14 [KO:K05414]
3449  IFNA16; interferon alpha 16 [KO:K05414]
3451  IFNA17; interferon alpha 17 [KO:K05414]
3452  IFNA21; interferon alpha 21 [KO:K05414]
3456  IFNB1; interferon beta 1 [KO:K05415]
10332  CLEC4M; C-type lectin domain family 4 member M [KO:K06563]
30835  CD209; CD209 molecule [KO:K06563]
23365  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
387  RHOA; ras homolog family member A [KO:K04513]
4046  LSP1; lymphocyte specific protein 1 [KO:K14957]
1263  PLK3; polo like kinase 3 [KO:K08862] [EC:2.7.11.21]
8844  KSR1; kinase suppressor of ras 1 [KO:K14958]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
7040  TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  TGFB3; transforming growth factor beta 3 [KO:K13377]
1594  CYP27B1; cytochrome P450 family 27 subfamily B member 1 [KO:K07438] [EC:1.14.15.18]
7421  VDR; vitamin D receptor [KO:K08539]
820  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
718  C3; complement C3 [KO:K03990]
1378  CR1; complement C3b/C4b receptor 1 (Knops blood group) [KO:K04011]
1379  CR1L; complement C3b/C4b receptor 1 like [KO:K04011]
3687  ITGAX; integrin subunit alpha X [KO:K06462]
3689  ITGB2; integrin subunit beta 2 [KO:K06464]
3684  ITGAM; integrin subunit alpha M [KO:K06461]
22925  PLA2R1; phospholipase A2 receptor 1 [KO:K06560]
4360  MRC1; mannose receptor C-type 1 [KO:K06560]
9902  MRC2; mannose receptor C-type 2 [KO:K06560]
8877  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
56848  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
810  CALML3; calmodulin like 3 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
801  CALM1; calmodulin 1 [KO:K02183]
163688  CALML6; calmodulin like 6 [KO:K02183]
51806  CALML5; calmodulin like 5 [KO:K02183]
91860  CALML4; calmodulin like 4 [KO:K02183]
5289  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
5868  RAB5A; RAB5A, member RAS oncogene family [KO:K07887]
5869  RAB5B; RAB5B, member RAS oncogene family [KO:K07888]
5878  RAB5C; RAB5C, member RAS oncogene family [KO:K07889]
8411  EEA1; early endosome antigen 1 [KO:K12478]
7879  RAB7A; RAB7A, member RAS oncogene family [KO:K07897]
1509  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
10312  TCIRG1; T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [KO:K02154]
23545  ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154]
50617  ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154]
535  ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154]
9114  ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146]
245972  ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146]
51606  ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]
537  ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662]
527  ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155]
533  ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661]
3916  LAMP1; lysosomal associated membrane protein 1 [KO:K06528]
3920  LAMP2; lysosomal associated membrane protein 2 [KO:K06528]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
11151  CORO1A; coronin 1A [KO:K13882]
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
2209  FCGR1A; Fc gamma receptor Ia [KO:K06498]
2212  FCGR2A; Fc gamma receptor IIa [KO:K06472]
2213  FCGR2B; Fc gamma receptor IIb [KO:K12560]
9103  FCGR2C; Fc gamma receptor IIc (gene/pseudogene) [KO:K16824]
2214  FCGR3A; Fc gamma receptor IIIa [KO:K06463]
2215  FCGR3B; Fc gamma receptor IIIb [KO:K06463]
Compound
C00076  Calcium cation
C00338  Lipopolysaccharide
C01194  1-Phosphatidyl-D-myo-inositol
C01561  Calcidiol
C01673  Calcitriol
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
C06124  Sphingosine 1-phosphate
C19190  Trehalose-6,6'-dibehenate
C21790  Mycobacterial trehalose dimycolate
G13101  Lipomannan
G13105  Triacylated phosphatidyl-myo-inositol pentamannoside
G13106  Triacylated phosphatidyl-myo-inositol hexamannoside
G13108  Triacylated phosphatidyl-myo-inositol dimannoside
G13109  Tetraacylated phosphatidyl-myo-inositol dimannoside
G13112  Tetraacylated phosphatidyl-myo-inositol hexamannoside
G13113  Tetraacylated phosphatidyl-myo-inositol pentamannoside
G13114  Lipoarabinomannan
G13115  Mannose-capped lipoarabinomannan
Reference
  Authors
Saiga H, Shimada Y, Takeda K
  Title
Innate immune effectors in mycobacterial infection.
  Journal
Clin Dev Immunol 2011:347594 (2011)
DOI:10.1155/2011/347594
Reference
  Authors
Dheda K, Schwander SK, Zhu B, van Zyl-Smit RN, Zhang Y
  Title
The immunology of tuberculosis: from bench to bedside.
  Journal
Respirology 15:433-50 (2010)
DOI:10.1111/j.1440-1843.2010.01739.x
Reference
  Authors
van Crevel R, Ottenhoff TH, van der Meer JW
  Title
Innate immunity to Mycobacterium tuberculosis.
  Journal
Clin Microbiol Rev 15:294-309 (2002)
DOI:10.1128/CMR.15.2.294-309.2002
Reference
  Authors
Torrelles JB, Azad AK, Henning LN, Carlson TK, Schlesinger LS
  Title
Role of C-type lectins in mycobacterial infections.
  Journal
Curr Drug Targets 9:102-12 (2008)
DOI:10.2174/138945008783502467
Reference
  Authors
Jo EK, Yang CS, Choi CH, Harding CV
  Title
Intracellular signalling cascades regulating innate immune responses to Mycobacteria: branching out from Toll-like receptors.
  Journal
Cell Microbiol 9:1087-98 (2007)
DOI:10.1111/j.1462-5822.2007.00914.x
Reference
  Authors
Marakalala MJ, Graham LM, Brown GD
  Title
The role of Syk/CARD9-coupled C-type lectin receptors in immunity to Mycobacterium tuberculosis infections.
  Journal
Clin Dev Immunol 2010:567571 (2010)
DOI:10.1155/2010/567571
Reference
  Authors
Koul A, Herget T, Klebl B, Ullrich A
  Title
Interplay between mycobacteria and host signalling pathways.
  Journal
Nat Rev Microbiol 2:189-202 (2004)
DOI:10.1038/nrmicro840
Reference
  Authors
Torrelles JB, Schlesinger LS
  Title
Diversity in Mycobacterium tuberculosis mannosylated cell wall determinants impacts adaptation to the host.
  Journal
Tuberculosis (Edinb) 90:84-93 (2010)
DOI:10.1016/j.tube.2010.02.003
Reference
  Authors
Briken V, Porcelli SA, Besra GS, Kremer L
  Title
Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response.
  Journal
Mol Microbiol 53:391-403 (2004)
DOI:10.1111/j.1365-2958.2004.04183.x
Reference
  Authors
Baena A, Porcelli SA
  Title
Evasion and subversion of antigen presentation by Mycobacterium tuberculosis.
  Journal
Tissue Antigens 74:189-204 (2009)
DOI:10.1111/j.1399-0039.2009.01301.x
Reference
  Authors
Flannagan RS, Cosio G, Grinstein S
  Title
Antimicrobial mechanisms of phagocytes and bacterial evasion strategies.
  Journal
Nat Rev Microbiol 7:355-66 (2009)
DOI:10.1038/nrmicro2128
Reference
  Authors
Pieters J
  Title
Mycobacterium tuberculosis and the macrophage: maintaining a balance.
  Journal
Cell Host Microbe 3:399-407 (2008)
DOI:10.1016/j.chom.2008.05.006
Reference
  Authors
Scherr N, Jayachandran R, Mueller P, Pieters J
  Title
Interference of Mycobacterium tuberculosis with macrophage responses.
  Journal
Indian J Exp Biol 47:401-6 (2009)
Reference
  Authors
Reith W, LeibundGut-Landmann S, Waldburger JM.
  Title
Regulation of MHC class II gene expression by the class II transactivator.
  Journal
Nat Rev Immunol 5:793-806 (2005)
DOI:10.1038/nri1708
Reference
  Authors
Rothfuchs AG, Bafica A, Feng CG, Egen JG, Williams DL, Brown GD, Sher A
  Title
Dectin-1 interaction with Mycobacterium tuberculosis leads to enhanced IL-12p40 production by splenic dendritic cells.
  Journal
J Immunol 179:3463-71 (2007)
DOI:10.4049/jimmunol.179.6.3463
Reference
  Authors
Master SS, Rampini SK, Davis AS, Keller C, Ehlers S, Springer B, Timmins GS, Sander P, Deretic V
  Title
Mycobacterium tuberculosis prevents inflammasome activation.
  Journal
Cell Host Microbe 3:224-32 (2008)
DOI:10.1016/j.chom.2008.03.003
Reference
  Authors
Shtrichman R, Samuel CE
  Title
The role of gamma interferon in antimicrobial immunity.
  Journal
Curr Opin Microbiol 4:251-9 (2001)
DOI:10.1016/S1369-5274(00)00199-5
Related
pathway
hsa04010  MAPK signaling pathway
hsa04210  Apoptosis
hsa04612  Antigen processing and presentation
hsa04620  Toll-like receptor signaling pathway
hsa04621  NOD-like receptor signaling pathway
hsa04630  JAK-STAT signaling pathway
KO pathway
ko05152   

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