KEGG   PATHWAY: btax05142
Entry
btax05142                   Pathway                                
Name
Chagas disease - Budorcas taxicolor (takin)
Description
Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease, also called American trypanosomiasis. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they invade diverse host cells including cardiomyocytes. Establishment of infection depends on various parasite molecules such as cruzipain, oligopeptidase B, and trans-sialidase that activate Ca2+ signaling. Internalized parasites escape from the parasitophorous vacuole using secreted pore-forming TcTOX molecule and replicate in the cytosol. Multiplied parasites eventually lyse infected host cells and are released in the circulation. During these events, the parasites manipulate host innate immunity and elicit cardiomyocyte hypertrophy. T lymphocyte responses are also disturbed.
Class
Human Diseases; Infectious disease: parasitic
Pathway map
btax05142  Chagas disease
btax05142

Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128052396  TLR4; toll-like receptor 4 [KO:K10160]
128050916  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
128062410  TLR2; toll-like receptor 2 [KO:K10159]
128049758  TLR6; toll-like receptor 6 [KO:K10169]
128048083  TLR9; toll-like receptor 9 [KO:K10161]
128049046  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
128069805  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
128048533  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
128060227  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
128064467  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
128051495  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128047244  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128049619  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128047426  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
128048391  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
128055294  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
128055801  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
128053951  FOS; protein c-Fos [KO:K04379]
128044447  JUN; transcription factor Jun [KO:K04448]
128069947  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
128067677  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
128068238  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
128066643  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
128049417  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
128068546  RELA; transcription factor p65 [KO:K04735]
128052625  interferon beta-2-like [KO:K05415]
128052626  interferon beta-2-like [KO:K05415]
128052627  interferon beta-2-like [KO:K05415]
128052628  interferon beta-2 [KO:K05415]
128052635  interferon beta-2-like [KO:K05415]
128052636  interferon beta-2-like [KO:K05415]
128052637  interferon beta-2-like [KO:K05415]
128052638  interferon beta-2-like [KO:K05415]
128052639  interferon beta-2-like [KO:K05415]
128052640  interferon beta-2-like [KO:K05415]
128052652  interferon beta-2-like [KO:K05415]
128064805  C-C motif chemokine 5 [KO:K12499]
128065365  C-C motif chemokine 2 [KO:K14624]
128056772  TNF; tumor necrosis factor [KO:K03156]
128050368  IL12A; interleukin-12 subunit alpha isoform X1 [KO:K05406]
128051514  IL12B; interleukin-12 subunit beta [KO:K05425]
128046952  IL6; interleukin-6 [KO:K05405]
128049958  CXCL8; interleukin-8 [KO:K10030]
128064804  C-C motif chemokine 3-like [KO:K05408]
128064806  C-C motif chemokine 3 [KO:K05408]
128064807  C-C motif chemokine 3-like [KO:K05408]
128064809  C-C motif chemokine 3-like [KO:K05408]
128056569  IL1B; interleukin-1 beta [KO:K04519]
128063523  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
128070222  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
128070224  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
128060694  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
128051169  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
128052002  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
128067781  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
128049472  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
128051757  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
128068193  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
128048506  IFNG; interferon gamma [KO:K04687]
128053263  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
128047334  IFNGR2; interferon gamma receptor 2 [KO:K05133]
128047668  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
128065005  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
128050332  complement C3 [KO:K03990]
128050333  complement C3-like [KO:K03990]
128050932  CALR; calreticulin [KO:K08057]
128043402  C1QA; complement C1q subcomponent subunit A isoform X1 [KO:K03986]
128043404  C1QB; complement C1q subcomponent subunit B [KO:K03987]
128043405  C1QC; complement C1q subcomponent subunit C [KO:K03988]
128061792  IL10; interleukin-10 [KO:K05443]
128063320  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
128061503  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
128053888  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
128064606  ACE; angiotensin-converting enzyme [KO:K01283] [EC:3.4.15.1]
128065386  angiotensin-converting enzyme-like protein Ace3 [KO:K01283] [EC:3.4.15.1]
128054455  KNG1; kininogen-1 [KO:K03898]
128066728  B2 bradykinin receptor-like isoform X1 [KO:K03916]
128052307  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
128050674  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
128052310  GNA14; guanine nucleotide-binding protein subunit alpha-14 [KO:K04636]
128051393  GNA15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637]
128058011  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
128058303  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
128054050  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
128068545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
128044413  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
128057155  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
128046449  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
128062941  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
128058250  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
128058829  neuroendocrine secretory protein 55 [KO:K04632]
128067338  GNAL; guanine nucleotide-binding protein G(olf) subunit alpha [KO:K04633]
128046764  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128048354  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
128051987  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
128067292  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
128069199  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
128061812  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
128067871  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128068641  FADD; FAS-associated death domain protein [KO:K02373]
128064775  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
128066790  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
128060506  T-cell surface glycoprotein CD3 delta chain [KO:K06450]
128060834  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
128060507  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
128045120  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
128062529  IL2; interleukin-2 [KO:K05429]
Compound
C00062  L-Arginine
C00076  Calcium cation
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:10234174
  Authors
Bogdan C, Rollinghoff M
  Title
How do protozoan parasites survive inside macrophages?
  Journal
Parasitol Today 15:22-8 (1999)
DOI:10.1016/S0169-4758(98)01362-3
Reference
PMID:17110955
  Authors
Gazzinelli RT, Denkers EY
  Title
Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.
  Journal
Nat Rev Immunol 6:895-906 (2006)
DOI:10.1038/nri1978
Reference
PMID:1717552
  Authors
Norris KA, Bradt B, Cooper NR, So M
  Title
Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor.
  Journal
J Immunol 147:2240-7 (1991)
Reference
PMID:16238097
  Authors
Aguilar L, Ramirez G, Valck C, Molina MC, Rojas A, Schwaeble W, Ferreira V, Ferreira A
  Title
F(ab')2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement.
  Journal
Biol Res 38:187-95 (2005)
DOI:10.4067/S0716-97602005000200008
Reference
PMID:15223603
  Authors
Campos MA, Gazzinelli RT
  Title
Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors.
  Journal
Mediators Inflamm 13:139-43 (2004)
DOI:10.1080/09511920410001713565
Reference
PMID:12427093
  Authors
Burleigh BA, Woolsey AM
  Title
Cell signalling and Trypanosoma cruzi invasion.
  Journal
Cell Microbiol 4:701-11 (2002)
DOI:10.1046/j.1462-5822.2002.00226.x
Reference
PMID:17651955
  Authors
Tarleton RL
  Title
Immune system recognition of Trypanosoma cruzi.
  Journal
Curr Opin Immunol 19:430-4 (2007)
DOI:10.1016/j.coi.2007.06.003
Reference
PMID:16175174
  Authors
Andrade LO, Andrews NW
  Title
The Trypanosoma cruzi-host-cell interplay: location, invasion, retention.
  Journal
Nat Rev Microbiol 3:819-23 (2005)
DOI:10.1038/nrmicro1249
Reference
PMID:12377585
  Authors
Tan H, Andrews NW
  Title
Don't bother to knock--the cell invasion strategy of Trypanosoma cruzi.
  Journal
Trends Parasitol 18:427-8 (2002)
DOI:10.1016/S1471-4922(02)02368-1
Reference
PMID:10066513
  Authors
Burleigh BA, Andrews NW
  Title
Signaling and host cell invasion by Trypanosoma cruzi.
  Journal
Curr Opin Microbiol 1:461-5 (1998)
DOI:10.1016/S1369-5274(98)80066-0
Reference
PMID:12377942
  Authors
Stempin C, Giordanengo L, Gea S, Cerban F
  Title
Alternative activation and increase of Trypanosoma cruzi survival in murine macrophages stimulated by cruzipain, a parasite antigen.
  Journal
J Leukoc Biol 72:727-34 (2002)
DOI:10.1189/jlb.72.4.727
Reference
PMID:16030288
  Authors
Burleigh BA
  Title
Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes?
  Journal
Sci STKE 2005:pe36 (2005)
DOI:10.1126/stke.2932005pe36
Reference
PMID:1396957
  Authors
Gazzinelli RT, Oswald IP, Hieny S, James SL, Sher A
  Title
The microbicidal activity of interferon-gamma-treated macrophages against Trypanosoma cruzi involves an L-arginine-dependent, nitrogen oxide-mediated mechanism inhibitable by interleukin-10 and transforming growth factor-beta.
  Journal
Eur J Immunol 22:2501-6 (1992)
DOI:10.1002/eji.1830221006
Reference
PMID:2194668
  Authors
Andrews NW, Abrams CK, Slatin SL, Griffiths G
  Title
A T. cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH.
  Journal
Cell 61:1277-87 (1990)
DOI:10.1016/0092-8674(90)90692-8
Reference
PMID:9794425
  Authors
Freire-de-Lima CG, Nunes MP, Corte-Real S, Soares MP, Previato JO, Mendonca-Previato L, DosReis GA
  Title
Proapoptotic activity of a Trypanosoma cruzi ceramide-containing glycolipid turned on in host macrophages by IFN-gamma.
  Journal
J Immunol 161:4909-16 (1998)
Reference
PMID:15917295
  Authors
Hashimoto M, Nakajima-Shimada J, Aoki T
  Title
Trypanosoma cruzi posttranscriptionally up-regulates and exploits cellular FLIP for inhibition of death-inducing signal.
  Journal
Mol Biol Cell 16:3521-8 (2005)
DOI:10.1091/mbc.E04-12-1051
Reference
PMID:12874238
  Authors
Ropert C, Closel M, Chaves AC, Gazzinelli RT
  Title
Inhibition of a p38/stress-activated protein kinase-2-dependent phosphatase restores function of IL-1 receptor-associate kinase-1 and reverses Toll-like receptor 2- and 4-dependent tolerance of macrophages.
  Journal
J Immunol 171:1456-65 (2003)
DOI:10.4049/jimmunol.171.3.1456
Reference
PMID:12055254
  Authors
Ouaissi A, Guilvard E, Delneste Y, Caron G, Magistrelli G, Herbault N, Thieblemont N, Jeannin P
  Title
The Trypanosoma cruzi Tc52-released protein induces human dendritic cell maturation, signals via Toll-like receptor 2, and confers protection against lethal infection.
  Journal
J Immunol 168:6366-74 (2002)
DOI:10.4049/jimmunol.168.12.6366
Reference
PMID:12036740
  Authors
Teixeira MM, Gazzinelli RT, Silva JS
  Title
Chemokines, inflammation and Trypanosoma cruzi infection.
  Journal
Trends Parasitol 18:262-5 (2002)
DOI:10.1016/S1471-4922(02)02283-3
Reference
PMID:9190942
  Authors
Camargo MM, Almeida IC, Pereira ME, Ferguson MA, Travassos LR, Gazzinelli RT
  Title
Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages.
  Journal
J Immunol 158:5890-901 (1997)
Related
pathway
btax00330  Arginine and proline metabolism
btax04020  Calcium signaling pathway
btax04070  Phosphatidylinositol signaling system
btax04210  Apoptosis
btax04350  TGF-beta signaling pathway
btax04610  Complement and coagulation cascades
btax04620  Toll-like receptor signaling pathway
btax04670  Leukocyte transendothelial migration
KO pathway
ko05142   
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