KEGG   PATHWAY: ko05142Help
ko05142                     Pathway                                

Chagas disease (American trypanosomiasis)
Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. 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.
Human Diseases; Infectious diseases: Parasitic
BRITE hierarchy
Pathway map
ko05142  Chagas disease (American trypanosomiasis)

Ortholog table
H00358  Chagas disease
K10160  toll-like receptor 4
K05842  toll-like receptor adapter molecule 1
K13729  thiol-dependent reductase 1
K10159  toll-like receptor 2
K10169  toll-like receptor 6
K10161  toll-like receptor 9
K04729  myeloid differentiation primary response protein MyD88
K04730  interleukin-1 receptor-associated kinase 1 [EC:]
K04733  interleukin-1 receptor-associated kinase 4 [EC:]
K03175  TNF receptor-associated factor 6 [EC:]
K04430  mitogen-activated protein kinase kinase 4 [EC:]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K04441  p38 MAP kinase [EC:]
K04379  proto-oncogene protein c-fos
K04448  transcription factor AP-1
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:]
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K05415  interferon beta
K12499  C-C motif chemokine 5
K14624  C-C motif chemokine 2
K03156  tumor necrosis factor superfamily, member 2
K05406  interleukin 12A
K05425  interleukin 12B
K05405  interleukin 6
K10030  interleukin 8
K05408  C-C motif chemokine 3
K04519  interleukin 1 beta
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K04354  serine/threonine-protein phosphatase 2A regulatory subunit B
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:]
K04687  interferon gamma
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K03158  tumor necrosis factor receptor superfamily member 1A
K13241  nitric-oxide synthase, inducible [EC:]
K03990  complement component 3
K08057  calreticulin
K03986  complement C1q subcomponent subunit A
K03987  complement C1q subcomponent subunit B
K03988  complement C1q subcomponent subunit C
K08571  cruzipain [EC:]
K05443  interleukin 10
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K01283  peptidyl-dipeptidase A [EC:]
K03916  bradykinin receptor B2
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K04635  guanine nucleotide-binding protein subunit alpha-11
K04636  guanine nucleotide-binding protein subunit alpha-14
K04637  guanine nucleotide-binding protein subunit alpha-15
K05858  phosphatidylinositol phospholipase C, beta [EC:]
K01354  oligopeptidase B [EC:]
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K04534  guanine nucleotide-binding protein G(o) subunit alpha
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K04633  guanine nucleotide-binding protein G(olf) subunit alpha
K08041  adenylate cyclase 1 [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K04456  RAC serine/threonine-protein kinase [EC:]
K04388  TGF-beta receptor type-2 [EC:]
K04674  TGF-beta receptor type-1 [EC:]
K04500  mothers against decapentaplegic homolog 2/3
K03982  plasminogen activator inhibitor 1
K04389  tumor necrosis factor ligand superfamily member 6
K04390  tumor necrosis factor receptor superfamily member 6
K02373  FAS-associated death domain protein
K04398  caspase 8 [EC:]
K04724  CASP8 and FADD-like apoptosis regulator
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K06450  T-cell surface glycoprotein CD3 delta chain
K06451  T-cell surface glycoprotein CD3 epsilon chain
K06452  T-cell surface glycoprotein CD3 gamma chain
K06453  CD3Z antigen, zeta polypeptide
K05429  interleukin 2
C00062  L-Arginine
C00076  Calcium cation
C00306  Bradykinin
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Bogdan C, Rollinghoff M
How do protozoan parasites survive inside macrophages?
Parasitol Today 15:22-8 (1999)
Gazzinelli RT, Denkers EY
Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.
Nat Rev Immunol 6:895-906 (2006)
Norris KA, Bradt B, Cooper NR, So M
Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor.
J Immunol 147:2240-7 (1991)
Aguilar L, Ramirez G, Valck C, Molina MC, Rojas A, Schwaeble W, Ferreira V, Ferreira A
F(ab')2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement.
Biol Res 38:187-95 (2005)
Campos MA, Gazzinelli RT
Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors.
Mediators Inflamm 13:139-43 (2004)
Burleigh BA, Woolsey AM
Cell signalling and Trypanosoma cruzi invasion.
Cell Microbiol 4:701-11 (2002)
Tarleton RL
Immune system recognition of Trypanosoma cruzi.
Curr Opin Immunol 19:430-4 (2007)
Andrade LO, Andrews NW
The Trypanosoma cruzi-host-cell interplay: location, invasion, retention.
Nat Rev Microbiol 3:819-23 (2005)
Tan H, Andrews NW
Don't bother to knock--the cell invasion strategy of Trypanosoma cruzi.
Trends Parasitol 18:427-8 (2002)
Burleigh BA, Andrews NW
Signaling and host cell invasion by Trypanosoma cruzi.
Curr Opin Microbiol 1:461-5 (1998)
Stempin C, Giordanengo L, Gea S, Cerban F
Alternative activation and increase of Trypanosoma cruzi survival in murine macrophages stimulated by cruzipain, a parasite antigen.
J Leukoc Biol 72:727-34 (2002)
Burleigh BA
Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes?
Sci STKE 2005:pe36 (2005)
Gazzinelli RT, Oswald IP, Hieny S, James SL, Sher A
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.
Eur J Immunol 22:2501-6 (1992)
Andrews NW, Abrams CK, Slatin SL, Griffiths G
A T. cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH.
Cell 61:1277-87 (1990)
Freire-de-Lima CG, Nunes MP, Corte-Real S, Soares MP, Previato JO, Mendonca-Previato L, DosReis GA
Proapoptotic activity of a Trypanosoma cruzi ceramide-containing glycolipid turned on in host macrophages by IFN-gamma.
J Immunol 161:4909-16 (1998)
Hashimoto M, Nakajima-Shimada J, Aoki T
Trypanosoma cruzi posttranscriptionally up-regulates and exploits cellular FLIP for inhibition of death-inducing signal.
Mol Biol Cell 16:3521-8 (2005)
Ropert C, Closel M, Chaves AC, Gazzinelli RT
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.
J Immunol 171:1456-65 (2003)
Ouaissi A, Guilvard E, Delneste Y, Caron G, Magistrelli G, Herbault N, Thieblemont N, Jeannin P
The Trypanosoma cruzi Tc52-released protein induces human dendritic cell maturation, signals via Toll-like receptor 2, and confers protection against lethal infection.
J Immunol 168:6366-74 (2002)
Teixeira MM, Gazzinelli RT, Silva JS
Chemokines, inflammation and Trypanosoma cruzi infection.
Trends Parasitol 18:262-5 (2002)
Camargo MM, Almeida IC, Pereira ME, Ferguson MA, Travassos LR, Gazzinelli RT
Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages.
J Immunol 158:5890-901 (1997)
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