KEGG PATHWAY: hsa05142

PATHWAY: hsa05142

Entry

hsa05142                    Pathway

Name

Chagas disease - Homo sapiens (human)

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

hsa05142

Chagas disease

Disease

H00358

Chagas disease

Organism

Homo sapiens (human) [GN:hsa]

Gene

7099	TLR4; toll like receptor 4 [KO:K10160]

148022

TICAM1; TIR domain containing 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; MYD88 innate immune signal transduction adaptor [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 nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]

1147	CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]

3551	IKBKB; inhibitor of nuclear factor kappa B kinase subunit 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 [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 C3 [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]

3827	KNG1; kininogen 1 [KO:K03898]

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]

5296	PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]

8503	PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]

110117499

P3R3URF-PIK3R3; P3R3URF-PIK3R3 readthrough [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]

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]

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; CD3 delta subunit of T-cell receptor complex [KO:K06450]

916	CD3E; CD3 epsilon subunit of T-cell receptor complex [KO:K06451]

917	CD3G; CD3 gamma subunit of T-cell receptor complex [KO:K06452]

919	CD247; CD247 molecule [KO:K06453]

3558	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

PMID:10234174

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

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)
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

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)
DOI:10.4067/S0716-97602005000200008

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)
DOI:10.1080/09511920410001713565

Reference

PMID:12427093

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

PMID:17651955

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

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)
DOI:10.1038/nrmicro1249

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)
DOI:10.1016/S1471-4922(02)02368-1

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)
DOI:10.1016/S1369-5274(98)80066-0

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)
DOI:10.1189/jlb.72.4.727

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)
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

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)
DOI:10.1091/mbc.E04-12-1051

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)
DOI:10.4049/jimmunol.171.3.1456

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)
DOI:10.4049/jimmunol.168.12.6366

Reference

PMID:12036740

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

hsa00330

Arginine and proline metabolism

hsa04020

Calcium signaling pathway

hsa04070

Phosphatidylinositol signaling system

hsa04210

Apoptosis

hsa04350