KEGG   PATHWAY: hsa05142Help
Entry
hsa05142                    Pathway                                

Name
Chagas disease (American trypanosomiasis) - Homo sapiens (human)
Description
Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. 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 diseases
BRITE hierarchy
Pathway map
Chagas disease (American trypanosomiasis)
hsa05142

All organismsOrtholog table
Disease
H00358  
Chagas disease
Organism
Homo sapiens (human) [GN:hsa]
Gene
7099  
TLR4; toll like receptor 4 [KO:K10160]
148022  
TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
7097  
TLR2; toll like receptor 2 [KO:K10159]
10333  
TLR6; toll like receptor 6 [KO:K10169]
54106  
TLR9; toll like receptor 9 [KO:K10161]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
3654  
IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
51135  
IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
7189  
TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
6416  
MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
2353  
FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
3725  
JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
4792  
NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  
NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  
RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
3456  
IFNB1; interferon beta 1 [KO:K05415]
6352  
CCL5; C-C motif chemokine ligand 5 [KO:K12499]
6347  
CCL2; C-C motif chemokine ligand 2 [KO:K14624]
7124  
TNF; tumor necrosis factor [KO:K03156]
3592  
IL12A; interleukin 12A [KO:K05406]
3593  
IL12B; interleukin 12B [KO:K05425]
3569  
IL6; interleukin 6 [KO:K05405]
3576  
CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
6348  
CCL3; C-C motif chemokine ligand 3 [KO:K05408]
6349  
CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408]
414062  
CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408]
3553  
IL1B; interleukin 1 beta [KO:K04519]
5519  
PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
5518  
PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
5520  
PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
5521  
PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
5522  
PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
55844  
PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
5515  
PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
5516  
PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
3458  
IFNG; interferon gamma [KO:K04687]
3459  
IFNGR1; interferon gamma receptor 1 [KO:K05132]
3460  
IFNGR2; interferon gamma receptor 2 (interferon gamma transducer 1) [KO:K05133]
7132  
TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
4843  
NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
718  
C3; complement component 3 [KO:K03990]
811  
CALR; calreticulin [KO:K08057]
712  
C1QA; complement C1q A chain [KO:K03986]
713  
C1QB; complement C1q B chain [KO:K03987]
714  
C1QC; complement C1q C chain [KO:K03988]
3586  
IL10; interleukin 10 [KO:K05443]
7040  
TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  
TGFB3; transforming growth factor beta 3 [KO:K13377]
1636  
ACE; angiotensin I converting enzyme [KO:K01283] [EC:3.4.15.1]
624  
BDKRB2; bradykinin receptor B2 [KO:K03916]
2776  
GNAQ; G protein subunit alpha q [KO:K04634]
2767  
GNA11; G protein subunit alpha 11 [KO:K04635]
9630  
GNA14; G protein subunit alpha 14 [KO:K04636]
2769  
GNA15; G protein subunit alpha 15 [KO:K04637]
23236  
PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
2770  
GNAI1; G protein subunit alpha i1 [KO:K04630]
2773  
GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  
GNAI2; G protein subunit alpha i2 [KO:K04630]
2775  
GNAO1; G protein subunit alpha o1 [KO:K04534]
2778  
GNAS; GNAS complex locus [KO:K04632]
2774  
GNAL; G protein subunit alpha L [KO:K04633]
107  
ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
5295  
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
207  
AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
7048  
TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
7046  
TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
4087  
SMAD2; SMAD family member 2 [KO:K04500]
4088  
SMAD3; SMAD family member 3 [KO:K04500]
5054  
SERPINE1; serpin family E member 1 [KO:K03982]
356  
FASLG; Fas ligand [KO:K04389]
355  
FAS; Fas cell surface death receptor [KO:K04390]
8772  
FADD; Fas associated via death domain [KO:K02373]
841  
CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
8837  
CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
915  
CD3D; CD3d molecule [KO:K06450]
916  
CD3E; CD3e molecule [KO:K06451]
917  
CD3G; CD3g molecule [KO:K06452]
919  
CD247; CD247 molecule [KO:K06453]
3558  
IL2; interleukin 2 [KO:K05429]
Compound
C00062  
L-Arginine
C00076  
Calcium cation
C00306  
Bradykinin
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)
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)
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)
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)
Reference
  Authors
Burleigh BA, Woolsey AM
  Title
Cell signalling and Trypanosoma cruzi invasion.
  Journal
Cell Microbiol 4:701-11 (2002)
Reference
  Authors
Tarleton RL
  Title
Immune system recognition of Trypanosoma cruzi.
  Journal
Curr Opin Immunol 19:430-4 (2007)
Reference
  Authors
Andrade LO, Andrews NW
  Title
The Trypanosoma cruzi-host-cell interplay: location, invasion, retention.
  Journal
Nat Rev Microbiol 3:819-23 (2005)
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)
Reference
  Authors
Burleigh BA, Andrews NW
  Title
Signaling and host cell invasion by Trypanosoma cruzi.
  Journal
Curr Opin Microbiol 1:461-5 (1998)
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)
Reference
  Authors
Burleigh BA
  Title
Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes?
  Journal
Sci STKE 2005:pe36 (2005)
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)
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)
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)
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)
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)
Reference
  Authors
Teixeira MM, Gazzinelli RT, Silva JS
  Title
Chemokines, inflammation and Trypanosoma cruzi infection.
  Journal
Trends Parasitol 18:262-5 (2002)
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)
KO pathway
 

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