KEGG PATHWAY: hsa05142

PATHWAY: hsa05142

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

Pathway map

hsa05142

Chagas disease (American trypanosomiasis)

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, E3 ubiquitin protein ligase [KO:K03175]
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; FBJ murine osteosarcoma viral oncogene homolog [KO:K04379]
3725	JUN; jun proto-oncogene [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; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4790	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
3456	IFNB1; interferon, beta 1, fibroblast [KO:K05415]
6352	CCL5; chemokine (C-C motif) ligand 5 [KO:K12499]
6347	CCL2; chemokine (C-C motif) ligand 2 [KO:K14624]
7124	TNF; tumor necrosis factor [KO:K03156]
3592	IL12A; interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) [KO:K05406]
3593	IL12B; interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) [KO:K05425]
3569	IL6; interleukin 6 (interferon, beta 2) [KO:K05405]
3576	IL8; interleukin 8 [KO:K10030]
6348	CCL3; chemokine (C-C motif) ligand 3 [KO:K05408]
6349	CCL3L1; chemokine (C-C motif) ligand 3-like 1 [KO:K05408]
414062	CCL3L3; chemokine (C-C motif) ligand 3-like 3 [KO:K05408]
101060267	c-C motif chemokine 3-like; K05408 C-C motif chemokine 3 [KO:K05408]
3553	IL1B; interleukin 1, beta [KO:K04519]
5519	PPP2R1B; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
5518	PPP2R1A; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
5520	PPP2R2A; protein phosphatase 2, regulatory subunit B, alpha [KO:K04354]
5521	PPP2R2B; protein phosphatase 2, regulatory subunit B, beta [KO:K04354]
5522	PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
55844	PPP2R2D; protein phosphatase 2, regulatory subunit B, delta [KO:K04354]
5515	PPP2CA; protein phosphatase 2, catalytic subunit, alpha isozyme [KO:K04382] [EC:3.1.3.16]
5516	PPP2CB; protein phosphatase 2, catalytic subunit, beta isozyme [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; tumor necrosis factor receptor superfamily, member 1A [KO:K03158]
4843	NOS2; nitric oxide synthase 2, inducible [KO:K13241] [EC:1.14.13.39]
718	C3; complement component 3 [KO:K03990]
811	CALR; calreticulin [KO:K08057]
712	C1QA; complement component 1, q subcomponent, A chain [KO:K03986]
713	C1QB; complement component 1, q subcomponent, B chain [KO:K03987]
714	C1QC; complement component 1, q subcomponent, 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 (peptidyl-dipeptidase A) 1 [KO:K01283] [EC:3.4.15.1]
624	BDKRB2; bradykinin receptor B2 [KO:K03916]
2776	GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
2767	GNA11; guanine nucleotide binding protein (G protein), alpha 11 (Gq class) [KO:K04635]
9630	GNA14; guanine nucleotide binding protein (G protein), alpha 14 [KO:K04636]
2769	GNA15; guanine nucleotide binding protein (G protein), alpha 15 (Gq class) [KO:K04637]
23236	PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [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 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332	PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
2770	GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773	GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771	GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
2775	GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
2778	GNAS; GNAS complex locus [KO:K04632]
2774	GNAL; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, olfactory type [KO:K04633]
107	ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
5295	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [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; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
7048	TGFBR2; transforming growth factor, beta receptor II (70/80kDa) [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 peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 [KO:K03982]
356	FASLG; Fas ligand (TNF superfamily, member 6) [KO:K04389]
355	FAS; Fas (TNF receptor superfamily, member 6) [KO:K04390]
8772	FADD; Fas (TNFRSF6)-associated via death domain [KO:K02373]
841	CASP8; caspase 8, apoptosis-related cysteine peptidase [KO:K04398] [EC:3.4.22.61]
8837	CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
915	CD3D; CD3d molecule, delta (CD3-TCR complex) [KO:K06450]
916	CD3E; CD3e molecule, epsilon (CD3-TCR complex) [KO:K06451]
917	CD3G; CD3g molecule, gamma (CD3-TCR complex) [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

PMID:10234174

Authors

Bogdan C, Rollinghoff M

Title

How do protozoan parasites survive inside macrophages?

Journal

Parasitol Today 15:22-8 (1999)

Reference

PMID:17110955

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

PMID:16238097

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

PMID:15223603

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

PMID:12427093

Authors

Burleigh BA, Woolsey AM

Title

Cell signalling and Trypanosoma cruzi invasion.

Journal

Cell Microbiol 4:701-11 (2002)

Reference

PMID:17651955

Authors

Tarleton RL

Title

Immune system recognition of Trypanosoma cruzi.

Journal

Curr Opin Immunol 19:430-4 (2007)

Reference

PMID:16175174

Authors

Andrade LO, Andrews NW

Title

The Trypanosoma cruzi-host-cell interplay: location, invasion, retention.

Journal

Nat Rev Microbiol 3:819-23 (2005)

Reference

PMID:12377585

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

PMID:10066513

Authors

Burleigh BA, Andrews NW

Title

Signaling and host cell invasion by Trypanosoma cruzi.

Journal

Curr Opin Microbiol 1:461-5 (1998)

Reference

PMID:12377942

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

PMID:16030288

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

PMID:15917295

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

PMID:12874238

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

PMID:12055254

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

PMID:12036740

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

ko05142

All links

Ontology (2)   
   KEGG BRITE (2)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (105)   
   KEGG GENES (105)   
All databases (110)   

Download RDF

DBGET integrated database retrieval system