KEGG   PATHWAY: mpah05142
Entry
mpah05142                   Pathway                                
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: parasitic
Pathway map
mpah05142  Chagas disease
mpah05142

Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110323586  Tlr4; toll-like receptor 4 [KO:K10160]
110336092  Ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
110320724  Tlr2; toll-like receptor 2 [KO:K10159]
110330777  Tlr6; toll-like receptor 6 [KO:K10169]
110328554  Tlr9; toll-like receptor 9 [KO:K10161]
110327862  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
110313647  Irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
110334455  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
110318382  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110331563  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
110334495  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110337896  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110337946  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334829  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
110324365  Fos; proto-oncogene c-Fos isoform X1 [KO:K04379]
110323252  Jun; transcription factor AP-1 [KO:K04448]
110313464  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
110334538  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110336182  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110324484  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110319789  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110317041  Rela; transcription factor p65 [KO:K04735]
110323346  Ifnb1; interferon beta [KO:K05415]
110332476  Ccl5; C-C motif chemokine 5 [KO:K12499]
110332475  C-C motif chemokine 12 [KO:K14624]
110331924  C-C motif chemokine 2 [KO:K14624]
110335791  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
110320680  Il12a; interleukin-12 subunit alpha [KO:K05406]
110332403  Il12b; interleukin-12 subunit beta [KO:K05425]
110317140  Il6; interleukin-6 [KO:K05405]
110332246  C-C motif chemokine 3 [KO:K05408]
110319321  Il1b; interleukin-1 beta isoform X1 [KO:K04519]
110328279  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
110337932  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
110325313  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
110330369  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
110332843  Ppp2r2b; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
110318923  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
110336304  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
110331422  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
110326932  Ifng; interferon gamma [KO:K04687]
110338217  Ifngr1; interferon gamma receptor 1 [KO:K05132]
110330069  Ifngr2; interferon gamma receptor 2 [KO:K05133]
110316225  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110331408  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
110335652  C3; complement C3 [KO:K03990]
110337259  Calr; calreticulin [KO:K08057]
110323460  calreticulin-like isoform X1 [KO:K08057]
110323698  C1qa; complement C1q subcomponent subunit A [KO:K03986]
110323604  C1qb; complement C1q subcomponent subunit B [KO:K03987]
110323611  C1qc; complement C1q subcomponent subunit C [KO:K03988]
110322547  Il10; interleukin-10 [KO:K05443]
110336543  Tgfb1; transforming growth factor beta-1 isoform X1 [KO:K13375]
110321649  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
110324521  Tgfb3; transforming growth factor beta-3 [KO:K13377]
110331687  Ace; angiotensin-converting enzyme isoform X1 [KO:K01283] [EC:3.4.15.1]
110332456  angiotensin-converting enzyme-like [KO:K01283] [EC:3.4.15.1]
110329894  Kng1; kininogen-1 [KO:K03898]
110330025  kininogen-1-like [KO:K03898]
110324855  Bdkrb2; B2 bradykinin receptor isoform X1 [KO:K03916]
110336980  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110326239  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
110320782  Gna14; guanine nucleotide-binding protein subunit alpha-14 [KO:K04636]
110326812  Gna15; guanine nucleotide-binding protein subunit alpha-15 [KO:K04637]
110336671  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
110317815  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
110318415  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110319646  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110314435  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
110327202  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
110319821  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
110337832  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110317699  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
110317700  neuroendocrine secretory protein 55 [KO:K04632]
110332897  Gnal; guanine nucleotide-binding protein G(olf) subunit alpha isoform X1 [KO:K04633]
110330584  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110328811  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110336420  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
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]
110319750  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110327251  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110317258  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110324386  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110322284  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110327573  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
110322784  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110332834  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110313068  Serpine1; plasminogen activator inhibitor 1 [KO:K03982]
110322215  Faslg; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
110332797  Fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
110333124  Fadd; FAS-associated death domain protein [KO:K02373]
110321675  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
110321922  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
110316786  uncharacterized protein LOC110316786 [KO:K10785]
110328514  Cd3d; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
110328560  Cd3e; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
110328470  Cd3g; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
110322175  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
110320556  Il2; interleukin-2 [KO:K05429]
Compound
C00062  L-Arginine
C00076  Calcium cation
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
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
Parasitol Today 15:22-8 (1999)
DOI:10.1016/S0169-4758(98)01362-3
Reference
  Authors
Gazzinelli RT, Denkers EY
  Title
Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.
  Journal
Nat Rev Immunol 6:895-906 (2006)
DOI:10.1038/nri1978
Reference
PMID:1717552
  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
Biol Res 38:187-95 (2005)
DOI:10.4067/S0716-97602005000200008
Reference
  Authors
Campos MA, Gazzinelli RT
  Title
Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors.
  Journal
Mediators Inflamm 13:139-43 (2004)
DOI:10.1080/09511920410001713565
Reference
  Authors
Burleigh BA, Woolsey AM
  Title
Cell signalling and Trypanosoma cruzi invasion.
  Journal
Cell Microbiol 4:701-11 (2002)
DOI:10.1046/j.1462-5822.2002.00226.x
Reference
  Authors
Tarleton RL
  Title
Immune system recognition of Trypanosoma cruzi.
  Journal
Curr Opin Immunol 19:430-4 (2007)
DOI:10.1016/j.coi.2007.06.003
Reference
  Authors
Andrade LO, Andrews NW
  Title
The Trypanosoma cruzi-host-cell interplay: location, invasion, retention.
  Journal
Nat Rev Microbiol 3:819-23 (2005)
DOI:10.1038/nrmicro1249
Reference
  Authors
Tan H, Andrews NW
  Title
Don't bother to knock--the cell invasion strategy of Trypanosoma cruzi.
  Journal
Trends Parasitol 18:427-8 (2002)
DOI:10.1016/S1471-4922(02)02368-1
Reference
  Authors
Burleigh BA, Andrews NW
  Title
Signaling and host cell invasion by Trypanosoma cruzi.
  Journal
Curr Opin Microbiol 1:461-5 (1998)
DOI:10.1016/S1369-5274(98)80066-0
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
J Leukoc Biol 72:727-34 (2002)
DOI:10.1189/jlb.72.4.727
Reference
  Authors
Burleigh BA
  Title
Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes?
  Journal
Sci STKE 2005:pe36 (2005)
DOI:10.1126/stke.2932005pe36
Reference
PMID:1396957
  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
Eur J Immunol 22:2501-6 (1992)
DOI:10.1002/eji.1830221006
Reference
PMID:2194668
  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
Cell 61:1277-87 (1990)
DOI:10.1016/0092-8674(90)90692-8
Reference
PMID:9794425
  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
Mol Biol Cell 16:3521-8 (2005)
DOI:10.1091/mbc.E04-12-1051
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
J Immunol 171:1456-65 (2003)
DOI:10.4049/jimmunol.171.3.1456
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
J Immunol 168:6366-74 (2002)
DOI:10.4049/jimmunol.168.12.6366
Reference
  Authors
Teixeira MM, Gazzinelli RT, Silva JS
  Title
Chemokines, inflammation and Trypanosoma cruzi infection.
  Journal
Trends Parasitol 18:262-5 (2002)
DOI:10.1016/S1471-4922(02)02283-3
Reference
PMID:9190942
  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
mpah00330  Arginine and proline metabolism
mpah04020  Calcium signaling pathway
mpah04070  Phosphatidylinositol signaling system
mpah04210  Apoptosis
mpah04350  TGF-beta signaling pathway
mpah04610  Complement and coagulation cascades
mpah04620  Toll-like receptor signaling pathway
mpah04670  Leukocyte transendothelial migration
KO pathway
ko05142   
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