KEGG   PATHWAY: rno05152
Entry
rno05152                    Pathway                                
Name
Tuberculosis - Rattus norvegicus (rat)
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
rno05152  Tuberculosis
rno05152

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24835  Tnf; tumor necrosis factor [KO:K03156]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
246756  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
64625  Bid; BH3-interacting domain death agonist [KO:K04726]
24887  Bax; apoptosis regulator BAX [KO:K02159]
367149  Bax-ps1; apoptosis regulator BAX-like [KO:K02159]
681314  apoptosis regulator BAX-like [KO:K02159]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
120099910  cytochrome c, somatic-like [KO:K08738]
690675  Cycsl2; cytochrome c, somatic-like [KO:K08738]
679794  Cycsl1; cytochrome c, somatic-like [KO:K08738]
290019  Cycsl3; cytochrome c, somatic-like [KO:K08738]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
78963  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
25400  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
24246  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
24245  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515] [EC:2.7.11.17]
171140  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
25712  Ifng; interferon gamma precursor [KO:K04687]
116465  Ifngr1; interferon gamma receptor 1 precursor [KO:K05132]
360697  Ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
85483  Ciita; MHC class II transactivator isoform 2 [KO:K08060] [EC:2.7.11.1]
310659  Rfx5; DNA-binding protein RFX5 [KO:K08061]
306353  Rfxank; DNA-binding protein RFXANK [KO:K08062]
499617  Rfxap; regulatory factor X-associated protein [KO:K08063]
29508  Nfya; nuclear transcription factor Y subunit alpha isoform 2 [KO:K08064]
25336  Nfyb; nuclear transcription factor Y subunit beta [KO:K08065]
25337  Nfyc; nuclear transcription factor Y subunit gamma [KO:K08066]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
294274  RT1-DMa; RT1 class II, DM alpha precursor [KO:K06752]
294273  RT1-DMb; RT1 class II, DM beta precursor [KO:K06752]
24984  RT1-DOa; RT1 class II, locus DOa precursor [KO:K06752]
24986  RT1-Ha; RT1 class II, locus Ha precursor [KO:K06752]
294269  RT1-Da; RT1 class II, locus Da precursor [KO:K06752]
294270  RT1-Db1; rano class II histocompatibility antigen, D-1 beta chain precursor [KO:K06752]
309621  RT1-Ba; rano class II histocompatibility antigen, B alpha chain precursor [KO:K06752]
309622  RT1-Bb; rano class II histocompatibility antigen, B-1 beta chain precursor [KO:K06752]
365542  RT1-DOb; RT1 class II, DO beta isoform 1 [KO:K06752]
24981  RT1-Db2; RT1 class II, locus Db2 precursor [KO:K06752]
25599  Cd74; H-2 class II histocompatibility antigen gamma chain [KO:K06505]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
25325  Il10; interleukin-10 precursor [KO:K05443]
117539  Il10ra; interleukin-10 receptor subunit alpha precursor [KO:K05134]
304091  Il10rb; interleukin-10 receptor subunit beta precursor [KO:K05135]
50654  Ctss; cathepsin S preproprotein [KO:K01368] [EC:3.4.22.27]
450223  Clec4e; C-type lectin domain family 4 member E [KO:K10059]
25441  Fcer1g; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
502902  Clec7a; C-type lectin domain family 7 member A [KO:K10074]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
25155  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
64171  Card9; caspase recruitment domain-containing protein 9 [KO:K12794]
307366  Malt1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform 1 [KO:K07369] [EC:3.4.22.-]
83477  Bcl10; B-cell lymphoma/leukemia 10 [KO:K07368]
291912  Nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
362491  Ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
291671  Hspa9; stress-70 protein, mitochondrial [KO:K04043]
63868  Hspd1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
103694176  Hspd1l1; 60 kDa heat shock protein, mitochondrial-like [KO:K04077] [EC:5.6.1.7]
29469  Lbp; lipopolysaccharide-binding protein precursor [KO:K05399]
310553  Tlr2; toll-like receptor 2 precursor [KO:K10159]
305354  Tlr1; toll-like receptor 1 precursor [KO:K05398]
305353  Tlr6; toll-like receptor 6 [KO:K10169]
29260  Tlr4; toll-like receptor 4 precursor [KO:K10160]
60350  Cd14; monocyte differentiation antigen CD14 precursor [KO:K04391]
680127  Tirap; toll/interleukin-1 receptor domain-containing adapter protein [KO:K05403]
301059  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
300177  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
363520  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
362418  Irak2; interleukin-1 receptor-associated kinase-like 2 [KO:K04731] [EC:2.7.11.1]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24599  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
24498  Il6; interleukin-6 precursor [KO:K05405]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
29197  Il18; interleukin-18 [KO:K05482]
155140  Il23a; interleukin-23 subunit alpha precursor [KO:K05426]
24493  Il1a; interleukin-1 alpha [KO:K04383]
24494  Il1b; interleukin-1 beta [KO:K04519]
24253  Cebpb; CCAAT/enhancer-binding protein beta isoform LAP1 [KO:K10048]
25301  Cebpg; CCAAT/enhancer-binding protein gamma [KO:K10049]
338457  Tlr9; toll-like receptor 9 precursor [KO:K10161]
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
690894  Ifna1; interferon alpha family, gene 5 precursor [KO:K05414]
100912314  interferon alpha-1-like [KO:K05414]
502961  Ifna4l2; similar to Interferon alpha-1 precursor [KO:K05414]
500491  Ifna16l1; interferon, alpha 16-like 1 precursor [KO:K05414]
134487075  interferon alpha-1-like [KO:K05414]
134487077  interferon alpha-1-like [KO:K05414]
100911527  Ifna4l1; interferon alpha-11-like [KO:K05414]
100912356  interferon alpha-1-like precursor [KO:K05414]
502959  Ifna1l1; similar to put. precursor MuIFN-alpha 5 precursor [KO:K05414]
24481  Ifnb1; interferon beta precursor [KO:K05415]
288375  Cd209a; CD209a molecule [KO:K06563]
288378  Clec4m; CD209b antigen [KO:K06563]
288386  Cd209cl2; CD209 antigen-like protein C [KO:K06563]
304197  Cd209l1; CD209 antigen-like protein E [KO:K06563]
501797  Cd209e; CD209 antigen-like protein E [KO:K06563]
688750  Cd209f; CD209 antigen-like protein 2 [KO:K06563]
688858  Cd209al3; CD209 antigen-like protein E [KO:K06563]
363856  Cd209d; CD209d molecule [KO:K06563]
100363064  Cd209fl1; CD209 antigen-like protein E [KO:K06563]
688951  Cd209c; CD209 antigen-like protein C [KO:K06563]
367072  Arhgef12; rho guanine nucleotide exchange factor 12 [KO:K07532]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
361680  Lsp1; lymphocyte-specific protein 1 [KO:K14957]
58936  Plk3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
108348076  Ksr1; kinase suppressor of Ras 1 [KO:K14958]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
25717  Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377]
114700  Cyp27b1; 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial [KO:K07438] [EC:1.14.15.18]
24873  Vdr; vitamin D3 receptor [KO:K08539]
316010  Camp; cathelicidin antimicrobial peptide precursor [KO:K13916]
24232  C3; complement C3 precursor [KO:K03990]
54243  Cr1l; complement component receptor 1-like protein isoform 2 precursor [KO:K04011]
499271  Itgax; integrin alpha-X precursor [KO:K06462]
309684  Itgb2; integrin beta-2 precursor [KO:K06464]
25021  Itgam; integrin alpha-M precursor [KO:K06461]
291327  Mrc1; macrophage mannose receptor 1 precursor [KO:K06560]
295631  Pla2r1; secretory phospholipase A2 receptor precursor [KO:K06560]
498011  Mrc2; C-type mannose receptor 2 precursor [KO:K06560]
308589  Sphk2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
170897  Sphk1; sphingosine kinase 1 isoform b [KO:K04718] [EC:2.7.1.91]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
50663  Calm2; calmodulin-2 [KO:K02183]
65052  Pik3c3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
64633  Rab5a; ras-related protein Rab-5A [KO:K07887]
100361891  Rab5al1; ras-related protein Rab-5A [KO:K07887]
288779  Rab5b; ras-related protein Rab-5B [KO:K07888]
287709  Rab5c; ras-related protein Rab-5C [KO:K07889]
314764  Eea1; early endosome antigen 1 isoform X1 [KO:K12478]
29448  Rab7a; ras-related protein Rab-7a [KO:K07897]
171293  Ctsd; cathepsin D precursor [KO:K01379] [EC:3.4.23.5]
29757  Atp6v0a1; V-type proton ATPase 116 kDa subunit a 1 [KO:K02154]
296981  Atp6v0a4; V-type proton ATPase 116 kDa subunit a 4 [KO:K02154]
293650  Tcirg1; V-type proton ATPase 116 kDa subunit a 3 [KO:K02154]
116455  Atp6v0a2; V-type proton ATPase 116 kDa subunit a 2 [KO:K02154]
291969  Atp6v0d1; V-type proton ATPase subunit d 1 [KO:K02146]
297932  Atp6v0d2; V-type proton ATPase subunit d 2 [KO:K02146]
297797  Atp6v1h; V-type proton ATPase subunit H isoform 1 [KO:K02144]
83615  Atp6ap1; V-type proton ATPase subunit S1 precursor [KO:K03662]
170667  Atp6v0c; V-type proton ATPase 16 kDa proteolipid subunit c [KO:K02155]
298451  Atp6v0b; V-type proton ATPase 21 kDa proteolipid subunit c'' [KO:K03661]
24944  Lamp2; lysosome-associated membrane glycoprotein 2 precursor [KO:K06528]
25328  Lamp1; lysosome-associated membrane glycoprotein 1 precursor [KO:K06528]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
155151  Coro1a; coronin-1A [KO:K13882]
295279  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498]
498276  Fcgr2al1; Fc gamma receptor 2A like 1 [KO:K06472]
134481532  low affinity immunoglobulin gamma Fc region receptor III isoform X1 [KO:K06472]
289211  Fcgr2b; low affinity immunoglobulin gamma Fc region receptor II [KO:K12560]
116591  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor III isoform 1 [KO:K06463]
304966  Fcgr3a; low affinity immunoglobulin gamma Fc region receptor III-A precursor [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
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
Related
pathway
rno04010  MAPK signaling pathway
rno04210  Apoptosis
rno04612  Antigen processing and presentation
rno04620  Toll-like receptor signaling pathway
rno04621  NOD-like receptor signaling pathway
rno04630  JAK-STAT signaling pathway
KO pathway
ko05152   
LinkDB

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