Entry Name Chagas disease - Mus pahari (shrew mouse)
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 Mus pahari (shrew mouse) [GN:
mpah ]
Gene 110316225 Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
110318415 Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
110318923 Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354 ]
110319646 Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
110319750 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110319789 Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
110319821 Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
110320782 Gna14; guanine nucleotide-binding protein subunit alpha-14 [KO:K04636 ]
110322175 Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
110322215 Faslg; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389 ]
110322865 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
110323448 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110325313 Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354 ]
110326239 Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
110326812 Gna15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637 ]
110327202 Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
110327251 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110327862 Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
110328279 Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456 ]
110328811 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
110330369 Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354 ]
110331422 Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382 ] [EC:3.1.3.16 ]
110332797 Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
110332834 Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
110332843 Ppp2r2b; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354 ]
110332897 Gnal; guanine nucleotide-binding protein G(olf) subunit alpha isoform X1 [KO:K04633 ]
110336304 Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382 ] [EC:3.1.3.16 ]
110336420 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
110336671 Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
110337832 Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
110337932 Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456 ]
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 mpah04070 Phosphatidylinositol signaling system
mpah04610 Complement and coagulation cascades
mpah04620 Toll-like receptor signaling pathway
mpah04670 Leukocyte transendothelial migration
KO pathway
