KEGG PATHWAY: ko05142

PATHWAY: ko05142

Entry

ko05142                     Pathway

Name

Chagas disease

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

ko05142

Chagas disease

Disease

H00358

Chagas disease

Orthology

K00922

PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K01283

ACE, CD143; peptidyl-dipeptidase A [EC:3.4.15.1]

K01354

ptrB; oligopeptidase B [EC:3.4.21.83]

K02373

FADD; FAS-associated death domain protein

K02580

NFKB1; nuclear factor NF-kappa-B p105 subunit

K02649

PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K03156

TNF, TNFA; tumor necrosis factor superfamily, member 2

K03158

TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A

K03175

TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]

K03456

PPP2R1; serine/threonine-protein phosphatase 2A regulatory subunit A

K03898

KNG, BK; kininogen

K03916

BDKRB2; bradykinin receptor B2

K03982

SERPINE1, PAI1; plasminogen activator inhibitor 1

K03986

C1QA; complement C1q subcomponent subunit A

K03987

C1QB; complement C1q subcomponent subunit B

K03988

C1QG; complement C1q subcomponent subunit C

K03990

C3; complement component 3

K04354

PPP2R2; serine/threonine-protein phosphatase 2A regulatory subunit B

K04371

ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04379

FOS; proto-oncogene protein c-fos

K04382

PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]

K04388

TGFBR2; TGF-beta receptor type-2 [EC:2.7.11.30]

K04389

TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6

K04390

TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6

K04398

CASP8; caspase 8 [EC:3.4.22.61]

K04430

MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04441

P38; p38 MAP kinase [EC:2.7.11.24]

K04448

JUN; transcription factor AP-1

K04456

AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]

K04467

IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]

K04500

SMAD2; mothers against decapentaplegic homolog 2

K04519

IL1B; interleukin 1 beta

K04534

GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha

K04630

GNAI; guanine nucleotide-binding protein G(i) subunit alpha

K04632

GNAS; guanine nucleotide-binding protein G(s) subunit alpha

K04633

GNAL; guanine nucleotide-binding protein G(olf) subunit alpha

K04634

GNAQ; guanine nucleotide-binding protein G(q) subunit alpha

K04635

GNA11; guanine nucleotide-binding protein subunit alpha-11

K04636

GNA14; guanine nucleotide-binding protein subunit alpha-14

K04637

GNA15; guanine nucleotide-binding protein subunit alpha-15

K04674

TGFBR1, ALK5; TGF-beta receptor type-1 [EC:2.7.11.30]

K04687

IFNG; interferon gamma

K04724

CFLAR, FLIP; CASP8 and FADD-like apoptosis regulator

K04729

MYD88; myeloid differentiation primary response protein MyD88

K04730

IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]

K04733

IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]

K04734

NFKBIA; NF-kappa-B inhibitor alpha

K04735

RELA; transcription factor p65

K05132

IFNGR1, CD119; interferon gamma receptor 1

K05133

IFNGR2; interferon gamma receptor 2

K05405

IL6; interleukin 6

K05406

IL12A; interleukin 12A

K05408

CCL3; C-C motif chemokine 3

K05415

IFNB; interferon beta

K05425

IL12B; interleukin 12B

K05429

IL2; interleukin 2

K05443

IL10, CSIF; interleukin 10

K05842

TRIF; toll-like receptor adapter molecule 1

K05858

PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]

K06450

CD3D; T-cell surface glycoprotein CD3 delta chain

K06451

CD3E; T-cell surface glycoprotein CD3 epsilon chain

K06452

CD3G; T-cell surface glycoprotein CD3 gamma chain

K06453

CD3Z, CD247; CD3Z antigen, zeta polypeptide

K07209

IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]

K07210

IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma

K08041

ADCY1; adenylate cyclase 1 [EC:4.6.1.1]

K08057

CALR; calreticulin

K08571

E3.4.22.51; cruzipain [EC:3.4.22.51]

K10030

IL8, CXCL8; interleukin 8

K10159

TLR2, CD282; toll-like receptor 2

K10160

TLR4, CD284; toll-like receptor 4

K10161

TLR9, CD289; toll-like receptor 9

K10169

TLR6, CD286; toll-like receptor 6

K10784

TRAV; T cell receptor alpha chain V region

K10785

TRBV; T-cell receptor beta chain V region

K12499

CCL5; C-C motif chemokine 5

K13241

NOS2; nitric-oxide synthase, inducible [EC:1.14.13.39]

K13375

TGFB1; transforming growth factor beta-1

K13376

TGFB2; transforming growth factor beta-2

K13377

TGFB3; transforming growth factor beta-3

K13729

TCAC2, TC52; thiol-dependent reductase 1

K14624

CCL2, MCP1; C-C motif chemokine 2

K23590

CRP; complement regulatory protein

K23591

TS; trans-sialidase

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

ko00330

Arginine and proline metabolism

ko04020

Calcium signaling pathway

ko04070

Phosphatidylinositol signaling system

ko04210

Apoptosis

ko04350