Entry
Name
Chagas disease - Ochotona princeps (American pika)
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
Ochotona princeps (American pika) [GN:
opi ]
Gene
101524248 MYD88; myeloid differentiation primary response protein MyD88 isoform X2 [KO:K04729 ]
101531611 NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
101535531 PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456 ]
101518020 serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456 ]
101533099 PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354 ]
101518605 PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354 ]
101533552 PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354 ]
101527218 PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382 ] [EC:3.1.3.16 ]
101530319 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
101516556 TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376 ]
101517012 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
101518174 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
101518418 GNA15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637 ]
101524349 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
101524739 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
101520538 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
101525340 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
101516368 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
101531957 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
101524943 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
101525095 GNAL; guanine nucleotide-binding protein G(olf) subunit alpha isoform X1 [KO:K04633 ]
101532354 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
101517982 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101528030 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101519449 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101533851 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922 ] [EC:2.7.1.153 ]
101533024 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
101527810 SERPINE1; plasminogen activator inhibitor 1 isoform X3 [KO:K03982 ]
101528266 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
101528938 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
101529860 CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450 ]
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
opi00330 Arginine and proline metabolism
opi04070 Phosphatidylinositol signaling system
opi04610 Complement and coagulation cascades
opi04620 Toll-like receptor signaling pathway
opi04670 Leukocyte transendothelial migration
KO pathway
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