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 K03156 tumor necrosis factor superfamily, member 2 K03158 tumor necrosis factor receptor superfamily member 1A K03171 tumor necrosis factor receptor type 1-associated DEATH domain protein K02373 FAS-associated death domain protein K04398 caspase 8 [EC:3.4.22.61] K04400 caspase 10 [EC:3.4.22.63] K02187 caspase 3 [EC:3.4.22.56] K04726 BH3 interacting domain death agonist K02159 apoptosis regulator BAX K08738 cytochrome c K04399 caspase 9 [EC:3.4.22.62] K02084 apoptotic protease-activating factor K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] K02158 Bcl-2-antagonist of cell death K02161 apoptosis regulator Bcl-2 K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] K04687 interferon gamma K05132 interferon gamma receptor 1 K05133 interferon gamma receptor 2 K11217 Janus kinase 1 [EC:2.7.10.2] K04447 Janus kinase 2 [EC:2.7.10.2] K11220 signal transducer and activator of transcription 1 K08060 MHC class II transactivator [EC:2.7.11.1] K08061 regulatory factor X 5 K08062 regulatory factor X-associated ankyrin-containing protein K08063 regulatory factor X-associated protein K08064 nuclear transcription factor Y, alpha K08065 nuclear transcription Y subunit beta K08066 nuclear transcription factor Y, gamma K05870 cyclic AMP-responsive element-binding protein 1 K06752 MHC class II antigen K06505 CD74 antigen K04498 E1A/CREB-binding protein [EC:2.3.1.48] K05443 interleukin 10 K05134 interleukin 10 receptor alpha K05135 interleukin 10 receptor beta K01368 cathepsin S [EC:3.4.22.27] K10059 C-type lectin domain family 4 member E K07983 high affinity immunoglobulin epsilon receptor subunit gamma K10074 C-type lectin domain family 7 member A K05704 tyrosine-protein kinase Src [EC:2.7.10.2] K05855 spleen tyrosine kinase [EC:2.7.10.2] K12794 caspase recruitment domain-containing protein 9 K07369 mucosa-associated lymphoid tissue lymphoma translocation protein 1 [EC:3.4.22.-] K07368 B-cell CLL/lymphoma 10 K14952 UDP-MurNAc hydroxylase K10165 nucleotide-binding oligomerization domain-containing protein 2 K08846 receptor-interacting serine/threonine-protein kinase 2 [EC:2.7.11.1] K14953 ipoprotein LpqH K14954 lipoprotein LprG K14955 lipoprotein LprA K02040 phosphate transport system substrate-binding protein K04043 molecular chaperone DnaK K04077 chaperonin GroEL [EC:5.6.1.7] K14956 ESAT-6 family protein K05399 lipopolysaccharide-binding protein K10159 toll-like receptor 2 K05398 toll-like receptor 1 K10169 toll-like receptor 6 K10160 toll-like receptor 4 K04391 monocyte differentiation antigen CD14 K05403 toll-interleukin 1 receptor (TIR) domain-containing adaptor protein K04729 myeloid differentiation primary response protein MyD88 K04733 interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1] K04730 interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1] K04731 interleukin-1 receptor-associated kinase 2 [EC:2.7.11.1] K03175 TNF receptor-associated factor 6 [EC:2.3.2.27] K02580 nuclear factor NF-kappa-B p105 subunit K04735 transcription factor p65 K04441 p38 MAP kinase [EC:2.7.11.24] K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24] K13241 nitric-oxide synthase, inducible [EC:1.14.13.39] K05405 interleukin 6 K05406 interleukin 12A K05425 interleukin 12B K05482 interleukin 18 K05426 interleukin 23 subunit alpha K04383 interleukin 1 alpha K04519 interleukin 1 beta K10048 CCAAT/enhancer binding protein (C/EBP), beta K10049 CCAAT/enhancer binding protein (C/EBP), gamma K10161 toll-like receptor 9 K05414 interferon alpha K05415 interferon beta K06563 C-type lectin domain family 4 member L/M K07532 Rho guanine nucleotide exchange factor 12 K04513 Ras homolog gene family, member A K14957 lymphocyte-specific protein 1 K08862 polo-like kinase 3 [EC:2.7.11.21] K14958 kinase suppressor of Ras 1 K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] K13375 transforming growth factor beta-1 K13376 transforming growth factor beta-2 K13377 transforming growth factor beta-3 K07438 calcidiol 1-monooxygenase (25-hydroxyvitamin D3 1alpha-hydroxylase) [EC:1.14.15.18] K08539 vitamin D3 receptor K13916 cathelicidin antimicrobial peptide K03990 complement component 3 K04011 complement component (3b/4b) receptor 1 K06462 integrin alpha X K06464 integrin beta 2 K06461 integrin alpha M K06560 mannose receptor, C type K04718 sphingosine kinase [EC:2.7.1.91] K02183 calmodulin K00914 phosphatidylinositol 3-kinase [EC:2.7.1.137] K07887 Ras-related protein Rab-5A K07888 Ras-related protein Rab-5B K07889 Ras-related protein Rab-5C K12478 early endosome antigen 1 K07897 Ras-related protein Rab-7A K01379 cathepsin D [EC:3.4.23.5] K02154 V-type H+-transporting ATPase subunit a K02146 V-type H+-transporting ATPase subunit d K02144 V-type H+-transporting ATPase subunit H K03662 V-type H+-transporting ATPase S1 subunit K02155 V-type H+-transporting ATPase 16kDa proteolipid subunit K03661 V-type H+-transporting ATPase 21kDa proteolipid subunit K06528 lysosomal-associated membrane protein 1/2 K21302 phosphatidylinositol-3-phosphatase [EC:3.1.3.64] K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] K06268 serine/threonine-protein phosphatase 2B regulatory subunit K13882 coronin-1A K14949 serine/threonine-protein kinase PknG [EC:2.7.11.1] K06856 immunoglobulin heavy chain K06498 high affinity immunoglobulin gamma Fc receptor I K06472 low affinity immunoglobulin gamma Fc receptor II-a K12560 low affinity immunoglobulin gamma Fc receptor II-b K16824 low affinity immunoglobulin gamma Fc receptor II-c K06463 low affinity immunoglobulin gamma Fc receptor III 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 ///