ENTRY ko05152 Pathway NAME Tuberculosis 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 ko05152 Tuberculosis DISEASE H00342 Tuberculosis ORTHOLOGY K00914 PIK3C3, VPS34; phosphatidylinositol 3-kinase [EC:2.7.1.137] K01368 CTSS; cathepsin S [EC:3.4.22.27] K01379 CTSD; cathepsin D [EC:3.4.23.5] K02040 pstS; phosphate transport system substrate-binding protein K02084 APAF1; apoptotic protease-activating factor K02144 ATPeV1H; V-type H+-transporting ATPase subunit H K02146 ATPeV0D, ATP6D; V-type H+-transporting ATPase subunit d K02154 ATPeV0A, ATP6N; V-type H+-transporting ATPase subunit a K02155 ATPeV0C, ATP6L; V-type H+-transporting ATPase 16kDa proteolipid subunit K02158 BAD; Bcl-2-antagonist of cell death K02159 BAX; apoptosis regulator BAX K02161 BCL2; apoptosis regulator Bcl-2 K02183 CALM; calmodulin K02187 CASP3; caspase 3 [EC:3.4.22.56] K02373 FADD; FAS-associated death domain protein K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2 K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A K03171 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein K03175 TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27] K03661 ATPeV0B, ATP6F; V-type H+-transporting ATPase 21kDa proteolipid subunit K03662 ATPeVS1, ATP6S1; V-type H+-transporting ATPase S1 subunit K03990 C3; complement component 3 K04011 CR1, CD35; complement component (3b/4b) receptor 1 K04043 dnaK, HSPA9; molecular chaperone DnaK K04077 groEL, HSPD1, HSP60, CPN60; chaperonin GroEL [EC:5.6.1.7] K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] K04371 ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24] K04383 IL1A; interleukin 1 alpha K04391 CD14; monocyte differentiation antigen CD14 K04398 CASP8; caspase 8 [EC:3.4.22.61] K04399 CASP9; caspase 9 [EC:3.4.22.62] K04400 CASP10; caspase 10 [EC:3.4.22.63] K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24] K04441 P38; p38 MAP kinase [EC:2.7.11.24] K04447 JAK2; Janus kinase 2 [EC:2.7.10.2] K04456 AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1] K04498 EP300, CREBBP, KAT3; E1A/CREB-binding protein [EC:2.3.1.48] K04513 RHOA; Ras homolog gene family, member A K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] K04519 IL1B; interleukin 1 beta K04687 IFNG; interferon gamma K04718 SPHK; sphingosine kinase [EC:2.7.1.91] K04726 BID; BH3 interacting domain death agonist K04729 MYD88; myeloid differentiation primary response protein MyD88 K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1] K04731 IRAK2; interleukin-1 receptor-associated kinase 2 [EC:2.7.11.1] K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1] K04735 RELA; transcription factor p65 K05132 IFNGR1, CD119; interferon gamma receptor 1 K05133 IFNGR2; interferon gamma receptor 2 K05134 IL10RA, CD210A; interleukin 10 receptor alpha K05135 IL10RB, CD210B; interleukin 10 receptor beta K05398 TLR1, CD281; toll-like receptor 1 K05399 LBP; lipopolysaccharide-binding protein K05403 TIRAP; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein K05405 IL6; interleukin 6 K05406 IL12A; interleukin 12A K05414 IFNA; interferon alpha K05415 IFNB; interferon beta K05425 IL12B; interleukin 12B K05426 IL23A; interleukin 23 subunit alpha K05443 IL10, CSIF; interleukin 10 K05482 IL18, IL1F4; interleukin 18 K05704 SRC; tyrosine-protein kinase Src [EC:2.7.10.2] K05855 SYK; spleen tyrosine kinase [EC:2.7.10.2] K05870 CREB1; cyclic AMP-responsive element-binding protein 1 K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit K06461 ITGAM, CD11b; integrin alpha M K06462 ITGAX, CD11c; integrin alpha X K06463 FCGR3, CD16; low affinity immunoglobulin gamma Fc receptor III K06464 ITGB2, CD18; integrin beta 2 K06472 FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a K06498 FCGR1A, CD64; high affinity immunoglobulin gamma Fc receptor I K06505 CD74, DHLAG; CD74 antigen K06528 LAMP1_2, CD107; lysosomal-associated membrane protein 1/2 K06560 MRC, CD206, CD280; mannose receptor, C type K06563 CLEC4L_M, DC-SIGN, CD209, CD299; C-type lectin domain family 4 member L/M K06752 MHC2; MHC class II antigen K06856 IGH; immunoglobulin heavy chain K07368 BCL10; B-cell CLL/lymphoma 10 K07369 MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [EC:3.4.22.-] K07438 CYP27B1; calcidiol 1-monooxygenase (25-hydroxyvitamin D3 1alpha-hydroxylase) [EC:1.14.15.18] K07532 ARHGEF12, LARG; Rho guanine nucleotide exchange factor 12 K07887 RAB5A; Ras-related protein Rab-5A K07888 RAB5B; Ras-related protein Rab-5B K07889 RAB5C; Ras-related protein Rab-5C K07897 RAB7A; Ras-related protein Rab-7A K07983 FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma K08060 CIITA; MHC class II transactivator [EC:2.7.11.1] K08061 RFX5; regulatory factor X 5 K08062 RFXANK; regulatory factor X-associated ankyrin-containing protein K08063 RFXAP; regulatory factor X-associated protein K08064 NFYA, HAP2; nuclear transcription factor Y, alpha K08065 NFYB, HAP3; nuclear transcription Y subunit beta K08066 NFYC, HAP5; nuclear transcription factor Y, gamma K08539 VDR, NR1I1; vitamin D3 receptor K08738 CYC; cytochrome c K08846 RIPK2; receptor-interacting serine/threonine-protein kinase 2 [EC:2.7.11.1] K08862 PLK3, CNK; polo-like kinase 3 [EC:2.7.11.21] K10048 CEBPB; CCAAT/enhancer binding protein (C/EBP), beta K10049 CEBPG; CCAAT/enhancer binding protein (C/EBP), gamma K10059 CLEC4E, MINCLE; C-type lectin domain family 4 member E K10074 CLEC7A, DECTIN1, CD369; C-type lectin domain family 7 member A K10159 TLR2, CD282; toll-like receptor 2 K10160 TLR4, CD284; toll-like receptor 4 K10161 TLR9, CD289; toll-like receptor 9 K10165 NOD2, CARD15; nucleotide-binding oligomerization domain-containing protein 2 K10169 TLR6, CD286; toll-like receptor 6 K11217 JAK1; Janus kinase 1 [EC:2.7.10.2] K11220 STAT1; signal transducer and activator of transcription 1 K12478 EEA1; early endosome antigen 1 K12560 FCGR2B, CD32; low affinity immunoglobulin gamma Fc receptor II-b K12794 CARD9; caspase recruitment domain-containing protein 9 K13241 NOS2; nitric-oxide synthase, inducible [EC:1.14.13.39] K13375 TGFB1; transforming growth factor beta-1 K13376 TGFB2; transforming growth factor beta-2 K13377 TGFB3; transforming growth factor beta-3 K13882 CORO1A; coronin-1A K13916 CAMP, LL37; cathelicidin antimicrobial peptide K14949 pknG; serine/threonine-protein kinase PknG [EC:2.7.11.1] K14952 namH; UDP-MurNAc hydroxylase K14953 lpqH; ipoprotein LpqH K14954 lprG; lipoprotein LprG K14955 lprA; lipoprotein LprA K14956 esx, esat6, cfp10; ESAT-6 family protein K14957 LSP1; lymphocyte-specific protein 1 K14958 KSR1; kinase suppressor of Ras 1 K16824 FCGR2C, CD32; low affinity immunoglobulin gamma Fc receptor II-c K21302 sapM; phosphatidylinositol-3-phosphatase [EC:3.1.3.64] 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 PMID:21274449 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 PMID:20415982 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 PMID:11932234 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 PMID:18288961 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 PMID:17359235 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 PMID:21274433 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 PMID:15083155 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 PMID:20199890 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 PMID:15228522 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 PMID:19563525 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 PMID:19369951 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 PMID:18541216 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 PMID:19634703 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 PMID:16200082 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 PMID:17785780 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 PMID:18407066 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 PMID:11378475 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 REL_PATHWAY ko00571 Lipoarabinomannan (LAM) biosynthesis ko04010 MAPK signaling pathway ko04210 Apoptosis ko04612 Antigen processing and presentation ko04620 Toll-like receptor signaling pathway ko04621 NOD-like receptor signaling pathway ko04630 JAK-STAT signaling pathway ///