KEGG   PATHWAY: mpah05145
Entry
mpah05145                   Pathway                                
Name
Toxoplasmosis - Mus pahari (shrew mouse)
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
mpah05145  Toxoplasmosis
mpah05145

Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110326932  Ifng; interferon gamma [KO:K04687]
110338217  Ifngr1; interferon gamma receptor 1 [KO:K05132]
110330069  Ifngr2; interferon gamma receptor 2 [KO:K05133]
110322912  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
110316808  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
110321139  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
110329620  Ciita; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
110335630  class II histocompatibility antigen, M alpha chain [KO:K06752]
110335686  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
110335782  H-2 class II histocompatibility antigen, E-K alpha chain [KO:K06752]
110335853  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
110335947  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
110335433  H-2 class II histocompatibility antigen, A-S beta chain [KO:K06752]
110335519  H-2 class II histocompatibility antigen, I-E beta chain [KO:K06752]
110335565  H-2 class II histocompatibility antigen, A-B alpha chain [KO:K06752]
110335584  H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
110332389  immunity-related GTPase family M protein 1 [KO:K14139] [EC:3.6.5.-]
110332777  immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
110332193  immunity-related GTPase family M protein 1-like [KO:K14140]
110331408  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
110329809  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
110325925  toll-like receptor 11 [KO:K14142]
110327862  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
110313647  Irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
110334455  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
110318382  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110338656  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110334874  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
110338176  Tab2; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110331197  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
110331335  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
110334495  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110337896  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110337946  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334829  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334538  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110336182  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110313464  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
110324484  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110325994  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
110319789  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110317041  Rela; transcription factor p65 [KO:K04735]
110320680  Il12a; interleukin-12 subunit alpha [KO:K05406]
110332403  Il12b; interleukin-12 subunit beta [KO:K05425]
110335791  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
110321591  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110318630  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
110321877  baculoviral IAP repeat-containing protein 2 [KO:K16060]
110327576  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
110328081  baculoviral IAP repeat-containing protein 3 [KO:K16060]
110313538  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
110319542  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
110338918  Ly96; lymphocyte antigen 96 isoform X1 [KO:K05400]
110323586  Tlr4; toll-like receptor 4 [KO:K10160]
110335695  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
110335998  heat shock 70 kDa protein 1A [KO:K03283]
110327293  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
110320724  Tlr2; toll-like receptor 2 [KO:K10159]
110337991  Lama2; laminin subunit alpha-2 [KO:K05637]
110335407  Lama1; laminin subunit alpha-1 [KO:K05637]
110333444  Lama3; laminin subunit alpha-3 [KO:K06240]
110319686  Lama5; laminin subunit alpha-5 [KO:K06240]
110326140  Lama4; laminin subunit alpha-4 isoform X1 [KO:K06241]
110324954  Lamb1; laminin subunit beta-1 isoform X1 [KO:K05636]
110327357  Lamb2; laminin subunit beta-2 [KO:K06243]
110322146  Lamb3; laminin subunit beta-3 [KO:K06244]
110321144  Lamc1; laminin subunit gamma-1 [KO:K05635]
110321772  Lamc2; laminin subunit gamma-2 [KO:K06246]
110318223  Lamc3; laminin subunit gamma-3 [KO:K06247]
110317477  Itga6; integrin alpha-6 isoform X1 [KO:K06485]
110337225  Itgb1; integrin beta-1 isoform X1 [KO:K05719]
110327206  Ldlr; low-density lipoprotein receptor isoform X1 [KO:K12473]
110316225  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110321675  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
110336608  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110332378  cytochrome c-like [KO:K08738]
110316223  cytochrome c, somatic [KO:K08738]
110317786  cytochrome c, testis-specific [KO:K08738]
110323338  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
110314435  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
110327202  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
110319821  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
110337832  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110324300  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
110331970  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
110332042  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
110337888  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
110317258  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110324386  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110322284  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110326250  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110314146  Cd40lg; CD40 ligand [KO:K03161]
110318846  Cd40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
110325751  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
110328063  C-C chemokine receptor type 5 [KO:K04180]
110315917  Alox5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
110322547  Il10; interleukin-10 [KO:K05443]
110327772  Il10ra; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
110329837  Il10rb; interleukin-10 receptor subunit beta [KO:K05135]
110327406  Tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
110332765  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
110336543  Tgfb1; transforming growth factor beta-1 isoform X1 [KO:K13375]
110321649  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
110324521  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
mpah00590  Arachidonic acid metabolism
mpah04010  MAPK signaling pathway
mpah04144  Endocytosis
mpah04210  Apoptosis
mpah04620  Toll-like receptor signaling pathway
mpah04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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