Entry Name Chagas disease
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: parasiticBRITE hierarchy
Pathway map Ortholog table Disease Orthology K05842 toll-like receptor adapter molecule 1
K13729 thiol-dependent reductase 1
K04729 myeloid differentiation primary response protein MyD88
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
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:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K04734 NF-kappa-B inhibitor alpha
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
K03156 tumor necrosis factor superfamily, member 2
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:3.1.3.16 ]
K05132 interferon gamma receptor 1
K05133 interferon gamma receptor 2
K03158 tumor necrosis factor receptor superfamily member 1A
K23590 complement regulatory protein
K03986 complement C1q subcomponent subunit A
K03987 complement C1q subcomponent subunit B
K03988 complement C1q subcomponent subunit C
K13375 transforming growth factor beta-1
K13376 transforming growth factor beta-2
K13377 transforming growth factor beta-3
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
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
K23591 trans-sialidase [EC:3.2.1.-]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K04500 mothers against decapentaplegic homolog 2
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
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
Compound 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 Reference Authors Gazzinelli RT, Denkers EY
Title Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.
Journal Reference 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 Reference Authors Campos MA, Gazzinelli RT
Title Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors.
Journal Reference Authors Burleigh BA, Woolsey AM
Title Cell signalling and Trypanosoma cruzi invasion.
Journal Reference Authors Tarleton RL
Title Immune system recognition of Trypanosoma cruzi.
Journal Reference Authors Andrade LO, Andrews NW
Title The Trypanosoma cruzi-host-cell interplay: location, invasion, retention.
Journal Reference Authors Tan H, Andrews NW
Title Don't bother to knock--the cell invasion strategy of Trypanosoma cruzi.
Journal Reference Authors Burleigh BA, Andrews NW
Title Signaling and host cell invasion by Trypanosoma cruzi.
Journal 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 Reference Authors Burleigh BA
Title Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes?
Journal Reference 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 Reference 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 Reference 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 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 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 Reference Authors Teixeira MM, Gazzinelli RT, Silva JS
Title Chemokines, inflammation and Trypanosoma cruzi infection.
Journal Reference 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 ko00330 Arginine and proline metabolism
ko04070 Phosphatidylinositol signaling system
ko04610 Complement and coagulation cascades
ko04620 Toll-like receptor signaling pathway
ko04670 Leukocyte transendothelial migration
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