KEGG   PATHWAY: bbis05142
Entry
bbis05142                   Pathway                                
Name
Chagas disease - Bison bison bison (American bison)
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
bbis05142  Chagas disease
bbis05142

Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104994776  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
104979701  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104989153  TLR2; toll-like receptor 2 [KO:K10159]
104984011  TLR6; toll-like receptor 6 [KO:K10169]
104997145  TLR9; toll-like receptor 9 [KO:K10161]
104985366  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
104991529  LOW QUALITY PROTEIN: interleukin-1 receptor-associated kinase 1-like [KO:K04730] [EC:2.7.11.1]
105003529  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
104982477  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104990873  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
104998999  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104992939  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981526  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104986748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104995620  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104981967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104981977  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104994938  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
104994939  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105000057  FOS; proto-oncogene c-Fos [KO:K04379]
105000175  JUN; transcription factor AP-1 [KO:K04448]
105002719  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
104993223  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
104985237  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104994637  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
104987029  RELA; transcription factor p65 [KO:K04735]
105000961  IFNB1; interferon beta [KO:K05415]
105000962  interferon beta-2 [KO:K05415]
105000963  interferon beta-2-like [KO:K05415]
104983695  interferon beta-1 [KO:K05415]
104996149  interferon beta-2-like [KO:K05415]
105004018  CCL5; C-C motif chemokine 5 [KO:K12499]
105003994  C-C motif chemokine 2 [KO:K14624]
104983770  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104988502  IL12A; interleukin-12 subunit alpha [KO:K05406]
104999734  IL12B; interleukin-12 subunit beta [KO:K05425]
104987936  IL6; interleukin-6 [KO:K05405]
104987314  C-X-C motif chemokine 15-like [KO:K10030]
104987320  interleukin-8 [KO:K10030]
105004026  C-C motif chemokine 3-like [KO:K05408]
105004028  C-C motif chemokine 3 [KO:K05408]
105004031  C-C motif chemokine 3-like [KO:K05408]
104984411  IL1B; interleukin-1 beta [KO:K04519]
105005078  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
104982191  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
104994293  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
104988728  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
104996269  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
105002745  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
104991861  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
104987748  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
104995460  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
104989779  IFNG; interferon gamma [KO:K04687]
104991667  IFNGR1; interferon gamma receptor 1 [KO:K05132]
105004619  IFNGR2; interferon gamma receptor 2 [KO:K05133]
104992338  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105003971  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
104979920  C3; complement C3 [KO:K03990]
104999841  CALR; calreticulin [KO:K08057]
104981091  C1QA; complement C1q subcomponent subunit A [KO:K03986]
104981094  C1QB; complement C1q subcomponent subunit B [KO:K03987]
104981092  C1QC; complement C1q subcomponent subunit C [KO:K03988]
104998829  IL10; interleukin-10 [KO:K05443]
104995381  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
104998204  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
104991770  TGFB3; transforming growth factor beta-3 [KO:K13377]
105000614  ACE; angiotensin-converting enzyme [KO:K01283] [EC:3.4.15.1]
104998627  KNG1; kininogen-1 isoform X1 [KO:K03898]
104996977  BDKRB2; B2 bradykinin receptor [KO:K03916]
104996774  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
104979885  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
104996772  GNA14; guanine nucleotide-binding protein subunit alpha-14 isoform X1 [KO:K04636]
105005595  GNA15; guanine nucleotide-binding protein subunit alpha-15 isoform X1 [KO:K04637]
104987189  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
104994462  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104984484  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104984486  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104981671  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
104994506  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
104997186  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105004321  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
104989972  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
104989974  neuroendocrine secretory protein 55 [KO:K04632]
105002480  GNAL; guanine nucleotide-binding protein G(olf) subunit alpha [KO:K04633]
104980414  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
104998445  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104992716  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104994333  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
104999978  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105001799  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104996058  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104986245  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
104995356  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104989637  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
105003597  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104985407  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
104993728  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
104989326  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
104983114  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
104995820  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104987521  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
104986928  FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373]
105003655  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105003652  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
104999482  LOW QUALITY PROTEIN: uncharacterized protein LOC104999482 [KO:K10785]
104983199  uncharacterized protein LOC104983199 [KO:K10785]
104981365  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
104981364  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
104981366  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
104992961  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
105003236  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
bbis00330  Arginine and proline metabolism
bbis04020  Calcium signaling pathway
bbis04070  Phosphatidylinositol signaling system
bbis04210  Apoptosis
bbis04350  TGF-beta signaling pathway
bbis04610  Complement and coagulation cascades
bbis04620  Toll-like receptor signaling pathway
bbis04670  Leukocyte transendothelial migration
KO pathway
ko05142   
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