Entry Name Chagas disease - Macaca mulatta (rhesus monkey)
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 Disease Organism Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene 106992315 TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375 ]
114673806 GNAL; guanine nucleotide-binding protein G(olf) subunit alpha isoform X1 [KO:K04633 ]
574159 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
574234 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
574294 TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842 ]
574332 FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390 ]
574394 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534 ]
694747 IL12B; interleukin-12 subunit beta precursor [KO:K05425 ]
695118 PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382 ] [EC:3.1.3.16 ]
696494 MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
697581 SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500 ]
697814 CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453 ]
698996 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
699310 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
699467 CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451 ]
699520 PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354 ]
699582 CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450 ]
701237 IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210 ]
701951 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
703239 TGFB3; transforming growth factor beta-3 precursor [KO:K13377 ]
703780 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
705270 CD3G; T-cell surface glycoprotein CD3 gamma chain precursor [KO:K06452 ]
705448 GNA14; guanine nucleotide-binding protein subunit alpha-14 [KO:K04636 ]
705680 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
706988 PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354 ]
707310 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
707540 TGFB2; transforming growth factor beta-2 precursor [KO:K13376 ]
708477 C1QA; complement C1q subcomponent subunit A [KO:K03986 ]
708589 C1QC; complement C1q subcomponent subunit C precursor [KO:K03988 ]
708606 FADD; FAS-associated death domain protein [KO:K02373 ]
708940 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630 ]
709511 CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467 ] [EC:2.7.11.10 ]
709959 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
710324 NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
710326 PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382 ] [EC:3.1.3.16 ]
710387 PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456 ]
710552 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
711023 PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354 ]
711920 PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354 ]
713883 SERPINE1; plasminogen activator inhibitor 1 [KO:K03982 ]
715919 RELA; transcription factor p65 isoform X1 [KO:K04735 ]
716098 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
717764 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
718155 MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430 ] [EC:2.7.12.2 ]
718307 C1QB; complement C1q subcomponent subunit B [KO:K03987 ]
718387 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
718418 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858 ] [EC:3.1.4.11 ]
719367 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
719929 PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456 ]
721649 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
721669 GNA15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637 ]
722033 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
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 mcc00330 Arginine and proline metabolism
mcc04070 Phosphatidylinositol signaling system
mcc04610 Complement and coagulation cascades
mcc04620 Toll-like receptor signaling pathway
mcc04670 Leukocyte transendothelial migration
KO pathway
