Entry
Name
Chagas disease - Pongo abelii (Sumatran orangutan)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Pongo abelii (Sumatran orangutan) [GN:
pon ]
Gene
100460593 MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729 ]
100461595 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
100173260 PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456 ]
100437928 PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456 ]
100436819 PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X2 [KO:K04354 ]
100443527 PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354 ]
100174027 PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354 ]
100462193 PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354 ]
100461606 PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382 ] [EC:3.1.3.16 ]
100438667 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
100433850 C1QA; complement C1q subcomponent subunit A isoform X2 [KO:K03986 ]
100435212 C1QB; complement C1q subcomponent subunit B isoform X1 [KO:K03987 ]
100432946 C1QC; complement C1q subcomponent subunit C isoform X1 [KO:K03988 ]
100458686 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
100460338 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
100457952 GNA14; guanine nucleotide-binding protein subunit alpha-14 [KO:K04636 ]
100461441 GNA15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637 ]
100458716 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100460060 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100434502 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100461961 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100456074 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
100172679 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
100458137 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
100454626 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
100442753 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X3 [KO:K04632 ]
100453901 GNAL; guanine nucleotide-binding protein G(olf) subunit alpha isoform X2 [KO:K04633 ]
100174298 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
100173589 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
100437617 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100432846 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100453779 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
103889133 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100435876 SERPINE1; LOW QUALITY PROTEIN: plasminogen activator inhibitor 1 [KO:K03982 ]
100461418 FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389 ]
100440370 CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X2 [KO:K06452 ]
100458470 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
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 pathway
pon00330 Arginine and proline metabolism
pon04070 Phosphatidylinositol signaling system
pon04610 Complement and coagulation cascades
pon04620 Toll-like receptor signaling pathway
pon04670 Leukocyte transendothelial migration
KO pathway
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