KEGG PATHWAY: hsa05145

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PATHWAY: hsa05145

Entry

hsa05145                    Pathway

Name

Toxoplasmosis - Homo sapiens (human)

Description

Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host.

Class

Human Diseases; Infectious disease: parasitic

Pathway map

hsa05145

Toxoplasmosis

Disease

H00435

Toxoplasmosis

Organism

Homo sapiens (human) [GN:hsa]

Gene

3458	IFNG; interferon gamma [KO:K04687]

3459	IFNGR1; interferon gamma receptor 1 [KO:K05132]

3460	IFNGR2; interferon gamma receptor 2 [KO:K05133]

3716	JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]

3717	JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]

6772	STAT1; signal transducer and activator of transcription 1 [KO:K11220]

4261	CIITA; class II major histocompatibility complex transactivator [KO:K08060] [EC:2.7.11.1]

3108	HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]

3109	HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]

3111	HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]

3112	HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]

3113	HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]

3115	HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]

3117	HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]

3118	HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]

3119	HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]

3122	HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]

3123	HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]

3125	HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]

3126	HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]

3127	HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]

345611

IRGM; immunity related GTPase M [KO:K14139] [EC:3.6.5.-]

4843	NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]

8651	SOCS1; suppressor of cytokine signaling 1 [KO:K04694]

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]

6885	MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]

10454

TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]

23118

TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404]

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]

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]

5606	MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]

5608	MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]

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]

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]

8517	IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]

4792	NFKBIA; NFKB inhibitor alpha [KO:K04734]

4793	NFKBIB; NFKB inhibitor beta [KO:K02581]

4790	NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]

5970	RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]

3592	IL12A; interleukin 12A [KO:K05406]

3593	IL12B; interleukin 12B [KO:K05425]

7124	TNF; tumor necrosis factor [KO:K03156]

596	BCL2; BCL2 apoptosis regulator [KO:K02161]

598	BCL2L1; BCL2 like 1 [KO:K04570]

329	BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]

330	BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]

331	XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]

79444

BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]

23643

LY96; lymphocyte antigen 96 [KO:K05400]

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

3312	HSPA8; heat shock protein family A (Hsp70) member 8 [KO:K03283]

3303	HSPA1A; heat shock protein family A (Hsp70) member 1A [KO:K03283]

3305	HSPA1L; heat shock protein family A (Hsp70) member 1 like [KO:K03283]

3304	HSPA1B; heat shock protein family A (Hsp70) member 1B [KO:K03283]

3310	HSPA6; heat shock protein family A (Hsp70) member 6 [KO:K03283]

7097	TLR2; toll like receptor 2 [KO:K10159]

284217

LAMA1; laminin subunit alpha 1 [KO:K05637]

3908	LAMA2; laminin subunit alpha 2 [KO:K05637]

3909	LAMA3; laminin subunit alpha 3 [KO:K06240]

3911	LAMA5; laminin subunit alpha 5 [KO:K06240]

3910	LAMA4; laminin subunit alpha 4 [KO:K06241]

3912	LAMB1; laminin subunit beta 1 [KO:K05636]

3913	LAMB2; laminin subunit beta 2 [KO:K06243]

3914	LAMB3; laminin subunit beta 3 [KO:K06244]

22798

LAMB4; laminin subunit beta 4 [KO:K06245]

3915	LAMC1; laminin subunit gamma 1 [KO:K05635]

3918	LAMC2; laminin subunit gamma 2 [KO:K06246]

10319

LAMC3; laminin subunit gamma 3 [KO:K06247]

3655	ITGA6; integrin subunit alpha 6 [KO:K06485]

3688	ITGB1; integrin subunit beta 1 [KO:K05719]

3949	LDLR; low density lipoprotein receptor [KO:K12473]

7132	TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]

841	CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]

836	CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]

54205

CYCS; cytochrome c, somatic [KO:K08738]

842	CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]

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]

5294	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]

23533

PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]

146850

PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]

5170	PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]

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]

572	BAD; BCL2 associated agonist of cell death [KO:K02158]

959	CD40LG; CD40 ligand [KO:K03161]

958	CD40; CD40 molecule [KO:K03160]

10105

PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]

1234	CCR5; C-C motif chemokine receptor 5 [KO:K04180]

240	ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]

3586	IL10; interleukin 10 [KO:K05443]

3587	IL10RA; interleukin 10 receptor subunit alpha [KO:K05134]

3588	IL10RB; interleukin 10 receptor subunit beta [KO:K05135]

7297	TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]

6774	STAT3; signal transducer and activator of transcription 3 [KO:K04692]

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]

Compound

C00076

Calcium cation

C05981

Phosphatidylinositol-3,4,5-trisphosphate

C06314

Lipoxin A4

Reference

PMID:15639739

Authors

Denkers EY, Butcher BA

Title

Sabotage and exploitation in macrophages parasitized by intracellular protozoans.

Journal

Trends Parasitol 21:35-41 (2005)
DOI:10.1016/j.pt.2004.10.004

Reference

PMID:14642303

Authors

Denkers EY

Title

From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii.

Journal

FEMS Immunol Med Microbiol 39:193-203 (2003)
DOI:10.1016/S0928-8244(03)00279-7

Reference

PMID:19744886

Authors

Pollard AM, Knoll LJ, Mordue DG

Title

The role of specific Toxoplasma gondii molecules in manipulation of innate immunity.

Journal

Trends Parasitol 25:491-4 (2009)
DOI:10.1016/j.pt.2009.07.009

Reference

PMID:19891610

Authors

Leng J, Butcher BA, Denkers EY

Title

Dysregulation of macrophage signal transduction by Toxoplasma gondii: past progress and recent advances.

Journal

Parasite Immunol 31:717-28 (2009)
DOI:10.1111/j.1365-3024.2009.01122.x

Reference

PMID:18775432

Authors

Miller CM, Boulter NR, Ikin RJ, Smith NC

Title

The immunobiology of the innate response to Toxoplasma gondii.

Journal

Int J Parasitol 39:23-39 (2009)
DOI:10.1016/j.ijpara.2008.08.002

Reference

PMID:12580944

Authors

Denkers EY, Kim L, Butcher BA

Title

In the belly of the beast: subversion of macrophage proinflammatory signalling cascades during Toxoplasma gondii infection.

Journal

Cell Microbiol 5:75-83 (2003)
DOI:10.1046/j.1462-5822.2003.00258.x

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:17024357

Authors

Lang C, Gross U, Luder CG

Title

Subversion of innate and adaptive immune responses by Toxoplasma gondii.

Journal

Parasitol Res 100:191-203 (2007)
DOI:10.1007/s00436-006-0306-9

Reference

PMID:19400868

Authors

Blader IJ, Saeij JP

Title

Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence.

Journal

APMIS 117:458-76 (2009)
DOI:10.1111/j.1600-0463.2009.02453.x

Reference

PMID:18059289

Authors

Boothroyd JC, Dubremetz JF

Title

Kiss and spit: the dual roles of Toxoplasma rhoptries.

Journal

Nat Rev Microbiol 6:79-88 (2008)
DOI:10.1038/nrmicro1800

Reference

PMID:15361242

Authors

Denkers EY, Butcher BA, Del Rio L, Kim L

Title

Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signaling cascades during intracellular Toxoplasma gondii infection.

Journal

Immunol Rev 201:191-205 (2004)
DOI:10.1111/j.0105-2896.2004.00180.x

Reference

PMID:18617274

Authors

Yarovinsky F

Title

Toll-like receptors and their role in host resistance to Toxoplasma gondii.

Journal

Immunol Lett 119:17-21 (2008)
DOI:10.1016/j.imlet.2008.05.007

Reference

PMID:14987366

Authors

Coppens I, Joiner KA

Title

Parasitehost cell interactions in toxoplasmosis: new avenues for intervention?

Journal

Expert Rev Mol Med 2001:1-20 (2001)
DOI:10.1017/S1462399401002277

Reference

PMID:12106793

Authors

Aliberti J, Sher A

Title

Role of G-protein-coupled signaling in the induction and regulation of dendritic cell function by Toxoplasma gondii.

Journal

Microbes Infect 4:991-7 (2002)
DOI:10.1016/S1286-4579(02)01618-0

Reference

PMID:12857995

Authors

Sher A, Collazzo C, Scanga C, Jankovic D, Yap G, Aliberti J

Title

Induction and regulation of IL-12-dependent host resistance to Toxoplasma gondii.

Journal

Immunol Res 27:521-8 (2003)
DOI:10.1385/IR:27:2-3:521

Reference

PMID:10525166

Authors

Bonhomme A, Bouchot A, Pezzella N, Gomez J, Le Moal H, Pinon JM

Title

Signaling during the invasion of host cells by Toxoplasma gondii.

Journal

FEMS Microbiol Rev 23:551-61 (1999)
DOI:10.1111/j.1574-6976.1999.tb00413.x

Reference

PMID:18327664

Authors

Laliberte J, Carruthers VB

Title

Host cell manipulation by the human pathogen Toxoplasma gondii.

Journal

Cell Mol Life Sci 65:1900-15 (2008)
DOI:10.1007/s00018-008-7556-x

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:16339966

Authors

Molestina RE, Sinai AP

Title

Host and parasite-derived IKK activities direct distinct temporal phases of NF-kappaB activation and target gene expression following Toxoplasma gondii infection.

Journal

J Cell Sci 118:5785-96 (2005)
DOI:10.1242/jcs.02709

Related
pathway

hsa00590

Arachidonic acid metabolism

hsa04010

MAPK signaling pathway

hsa04144

Endocytosis

hsa04210

Apoptosis

hsa04620

Toll-like receptor signaling pathway

hsa04630

JAK-STAT signaling pathway

KO pathway

ko05145

All links

Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (111)   
   KEGG GENES (111)   
All databases (113)   

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