Entry Name Chagas disease - Pteropus alecto (black flying fox)
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 Organism Pteropus alecto (black flying fox) [GN:
pale ]
Gene 102890488 MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
102880692 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
102894487 PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456 ]
102888699 PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456 ]
102888692 PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354 ]
102882824 PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354 ]
102892945 PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354 ]
102885289 PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382 ] [EC:3.1.3.16 ]
102885752 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
102877919 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
102888619 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
102899020 GNA14; guanine nucleotide-binding protein subunit alpha-14 [KO:K04636 ]
102888860 GNA15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637 ]
102885207 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
102892785 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
102885642 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
102898665 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
102884654 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534 ]
102889764 guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632 ]
102886226 GNAL; guanine nucleotide-binding protein G(olf) subunit alpha isoform X1 [KO:K04633 ]
102879163 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
102891637 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649 ]
102879453 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
102889227 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
102880320 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102889576 PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102883204 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
102879561 FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390 ]
102898217 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
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 pale04070 Phosphatidylinositol signaling system
pale04610 Complement and coagulation cascades
pale04620 Toll-like receptor signaling pathway
pale04670 Leukocyte transendothelial migration
KO pathway LinkDB All DBs
