KEGG   PATHWAY: tmu05142
Entry
tmu05142                    Pathway                                
Name
Chagas disease - Trichechus manatus latirostris (Florida manatee)
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
tmu05142  Chagas disease
tmu05142

Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101353470  toll-like receptor 4 [KO:K10160]
101358234  TIR domain-containing adapter molecule 1 [KO:K05842]
101342847  toll-like receptor 2 [KO:K10159]
101357994  toll-like receptor 6 [KO:K10169]
101351541  toll-like receptor 9 isoform X1 [KO:K10161]
101341326  myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
101350273  interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
101349224  interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101345331  TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101349700  dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
101351734  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101351967  mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
101343546  mitogen-activated protein kinase 8 isoform X4 [KO:K04440] [EC:2.7.11.24]
101340589  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101358526  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101352466  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101347350  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101361614  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101361872  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101357016  proto-oncogene c-Fos [KO:K04379]
101361653  transcription factor AP-1 [KO:K04448]
101347574  NF-kappa-B essential modulator isoform X1 [KO:K07210]
101341290  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101351256  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101355353  NF-kappa-B inhibitor alpha [KO:K04734]
101351866  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101361706  transcription factor p65 [KO:K04735]
101349610  interferon beta [KO:K05415]
101352479  C-C motif chemokine 5 [KO:K12499]
101358871  C-C motif chemokine 2 [KO:K14624]
101342656  TNF; tumor necrosis factor [KO:K03156]
101353752  interleukin-12 subunit alpha [KO:K05406]
101344352  interleukin-12 subunit beta [KO:K05425]
101351590  interleukin-6 [KO:K05405]
101358515  interleukin-8 [KO:K10030]
101361964  regakine-1-like [KO:K05408]
101340657  C-C motif chemokine 3-like [KO:K05408]
101340395  C-C motif chemokine 3-like [KO:K05408]
101359415  IL1B; interleukin-1 beta [KO:K04519]
101344236  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
101347357  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101347198  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
101343363  protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
101352293  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
101358479  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
101358337  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101350333  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
101346429  interferon gamma [KO:K04687]
101345582  interferon gamma receptor 1 isoform X1 [KO:K05132]
101361970  interferon gamma receptor 2 [KO:K05133]
101341867  tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101356579  nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
101350977  complement C3 [KO:K03990]
101354484  calreticulin [KO:K08057]
101348752  LOW QUALITY PROTEIN: calreticulin-like [KO:K08057]
101349199  complement C1q subcomponent subunit A isoform X2 [KO:K03986]
101348685  complement C1q subcomponent subunit B [KO:K03987]
101348943  complement C1q subcomponent subunit C [KO:K03988]
101342743  interleukin-10 [KO:K05443]
101342543  transforming growth factor beta-1 isoform X2 [KO:K13375]
101347669  transforming growth factor beta-2 isoform X1 [KO:K13376]
101358028  transforming growth factor beta-3 [KO:K13377]
101341729  angiotensin-converting enzyme-like protein Ace3 [KO:K01283] [EC:3.4.15.1]
101341987  angiotensin-converting enzyme-like [KO:K01283] [EC:3.4.15.1]
101357365  angiotensin-converting enzyme-like isoform X1 [KO:K01283] [EC:3.4.15.1]
101352995  kininogen-1 isoform X1 [KO:K03898]
101347252  B2 bradykinin receptor [KO:K03916]
101347192  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101345890  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101347445  guanine nucleotide-binding protein subunit alpha-14 [KO:K04636]
101352296  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101349967  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101344242  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101361375  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
101341952  guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101346092  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101343271  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101357613  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101361837  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
101348142  neuroendocrine secretory protein 55 [KO:K04632]
101346169  guanine nucleotide-binding protein G(olf) subunit alpha [KO:K04633]
101354868  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101351035  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101343804  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101347746  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101358678  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101346849  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101359658  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101360493  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101356099  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101350197  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101354258  TGF-beta receptor type-2 isoform X4 [KO:K04388] [EC:2.7.11.30]
101359953  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
101348656  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101348466  plasminogen activator inhibitor 1 [KO:K03982]
101344408  tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
101346704  tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
101352734  FAS-associated death domain protein [KO:K02373]
101344302  caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101343780  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
111819117  uncharacterized protein LOC111819117 [KO:K10784]
101361451  LOW QUALITY PROTEIN: uncharacterized protein LOC101361451 [KO:K10785]
105756611  uncharacterized protein LOC105756611 [KO:K10785]
101342429  uncharacterized protein LOC101342429 [KO:K10785]
101353008  T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
101359660  T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451]
101352744  T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
101345999  T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
101360180  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
tmu00330  Arginine and proline metabolism
tmu04020  Calcium signaling pathway
tmu04070  Phosphatidylinositol signaling system
tmu04210  Apoptosis
tmu04350  TGF-beta signaling pathway
tmu04610  Complement and coagulation cascades
tmu04620  Toll-like receptor signaling pathway
tmu04670  Leukocyte transendothelial migration
KO pathway
ko05142   
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