KEGG PATHWAY: hsa05145

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 diseases

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 (interferon gamma transducer 1) [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, 91kDa [KO:K11220]
4261	CIITA; class II, major histocompatibility complex, transactivator [KO:K08060]
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]
100507709	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
100507714	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
100509457	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
101060835	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
345611	IRGM; immunity-related GTPase family, M [KO:K14139] [EC:3.6.5.-]
4843	NOS2; nitric oxide synthase 2, inducible [KO:K13241] [EC:1.14.13.39]
8651	SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
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]
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; 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]
8517	IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792	NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4793	NFKBIB; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
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]
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]
7124	TNF; tumor necrosis factor [KO:K03156]
596	BCL2; B-cell CLL/lymphoma 2 [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]
79444	BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
112401	BIRC8; baculoviral IAP repeat containing 8 [KO:K16061]
23643	LY96; lymphocyte antigen 96 [KO:K05400]
7099	TLR4; toll-like receptor 4 [KO:K10160]
3312	HSPA8; heat shock 70kDa protein 8 [KO:K03283]
3303	HSPA1A; heat shock 70kDa protein 1A [KO:K03283]
3306	HSPA2; heat shock 70kDa protein 2 [KO:K03283]
3305	HSPA1L; heat shock 70kDa protein 1-like [KO:K03283]
3304	HSPA1B; heat shock 70kDa protein 1B [KO:K03283]
3310	HSPA6; heat shock 70kDa protein 6 (HSP70B') [KO:K03283]
7097	TLR2; toll-like receptor 2 [KO:K10159]
284217	LAMA1; laminin, alpha 1 [KO:K05637]
3908	LAMA2; laminin, alpha 2 [KO:K05637]
3909	LAMA3; laminin, alpha 3 [KO:K06240]
3911	LAMA5; laminin, alpha 5 [KO:K06240]
3910	LAMA4; laminin, alpha 4 [KO:K06241]
3912	LAMB1; laminin, beta 1 [KO:K05636]
3913	LAMB2; laminin, beta 2 (laminin S) [KO:K06243]
3914	LAMB3; laminin, beta 3 [KO:K06244]
22798	LAMB4; laminin, beta 4 [KO:K06245]
3915	LAMC1; laminin, gamma 1 (formerly LAMB2) [KO:K05635]
3918	LAMC2; laminin, gamma 2 [KO:K06246]
10319	LAMC3; laminin, gamma 3 [KO:K06247]
3655	ITGA6; integrin, alpha 6 [KO:K06485]
3688	ITGB1; integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) [KO:K05719]
3949	LDLR; low density lipoprotein receptor [KO:K12473]
7132	TNFRSF1A; tumor necrosis factor receptor superfamily, member 1A [KO:K03158]
841	CASP8; caspase 8, apoptosis-related cysteine peptidase [KO:K04398] [EC:3.4.22.61]
836	CASP3; caspase 3, apoptosis-related cysteine peptidase [KO:K02187] [EC:3.4.22.56]
54205	CYCS; cytochrome c, somatic [KO:K08738]
842	CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
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]
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]
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]
5163	PDK1; pyruvate dehydrogenase kinase, isozyme 1 [KO:K12077] [EC:2.7.11.2]
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]
572	BAD; BCL2-associated agonist of cell death [KO:K02158]
959	CD40LG; CD40 ligand [KO:K03161]
958	CD40; CD40 molecule, TNF receptor superfamily member 5 [KO:K03160]
10105	PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
1234	CCR5; chemokine (C-C motif) receptor 5 (gene/pseudogene) [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, alpha [KO:K05134]
3588	IL10RB; interleukin 10 receptor, beta [KO:K05135]
7297	TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
6774	STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [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)

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)

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)

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)

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)

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)

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: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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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: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)

KO pathway

ko05145

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Ontology (2)   
   KEGG BRITE (2)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (122)   
   KEGG GENES (122)   
All databases (127)   

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