KEGG   PATHWAY: oor05145
Entry
oor05145                    Pathway                                
Name
Toxoplasmosis - Orcinus orca (killer whale)
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
oor05145  Toxoplasmosis
oor05145

Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101282933  IFNG; interferon gamma [KO:K04687]
101276054  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101279441  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
101275383  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101272458  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101290378  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
101275987  SLA class II histocompatibility antigen, DQ haplotype D alpha chain isoform X2 [KO:K06752]
101287624  HLA class II histocompatibility antigen, DM beta chain isoform X3 [KO:K06752]
101287882  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
101277081  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
101276823  DLA class II histocompatibility antigen, DR-1 beta chain isoform X3 [KO:K06752]
101288385  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
101289225  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
101280638  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
101289479  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
101278425  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
101280639  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X2 [KO:K04730] [EC:2.7.11.1]
101283238  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101277553  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
101283961  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101282675  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
101284365  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101287701  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
101277656  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
101281228  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
101275666  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
101280413  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101269212  MAPK13; mitogen-activated protein kinase 13 isoform X7 [KO:K04441] [EC:2.7.11.24]
101269458  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101287579  mitogen-activated protein kinase 12 isoform X6 [KO:K04441] [EC:2.7.11.24]
101287833  mitogen-activated protein kinase 11 isoform X5 [KO:K04441] [EC:2.7.11.24]
101281072  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101285763  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101272428  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101289477  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101279981  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
101279857  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101270342  RELA; transcription factor p65 isoform X1 [KO:K04735]
101279088  IL12A; interleukin-12 subunit alpha [KO:K05406]
101272835  IL12B; interleukin-12 subunit beta [KO:K05425]
101269870  TNF; tumor necrosis factor [KO:K03156]
101276750  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101288063  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101276394  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
101276649  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101290359  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
101286499  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
101289671  LY96; lymphocyte antigen 96 isoform X2 [KO:K05400]
101282217  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
101278046  heat shock cognate 71 kDa protein [KO:K03283]
101283817  HSPA1B; heat shock 70 kDa protein 1B [KO:K03283]
101284066  heat shock 70 kDa protein 1B [KO:K03283]
101284311  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
101282770  LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
101284349  heat shock cognate 71 kDa protein-like [KO:K03283]
125963979  LOW QUALITY PROTEIN: heat shock 70 kDa protein 6-like [KO:K03283]
125965152  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
101276053  TLR2; toll-like receptor 2 [KO:K10159]
101290006  LAMA2; laminin subunit alpha-2 [KO:K05637]
101282490  LAMA1; laminin subunit alpha-1 [KO:K05637]
101274600  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
101284962  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
101278374  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
101278853  LAMB1; laminin subunit beta-1 [KO:K05636]
101271226  LAMB2; laminin subunit beta-2 isoform X2 [KO:K06243]
101284932  LAMB3; laminin subunit beta-3 [KO:K06244]
101282409  LAMC1; laminin subunit gamma-1 [KO:K05635]
101282661  LAMC2; laminin subunit gamma-2 isoform X1 [KO:K06246]
101280646  LAMC3; laminin subunit gamma-3 isoform X2 [KO:K06247]
101271340  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
101283510  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
101283356  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
101282502  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101281780  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101289847  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
105747906  cytochrome c-like [KO:K08738]
101283052  cytochrome c [KO:K08738]
101275631  cytochrome c-like [KO:K08738]
105747703  cytochrome c 2 [KO:K08738]
101272869  cytochrome c-like [KO:K08738]
117203203  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
101271677  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
101276500  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101277471  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101271719  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101284566  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101281782  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
101275916  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
101275667  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101270868  PDPK1; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101272095  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101288103  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101273316  AKT1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101274967  BAD; bcl2-associated agonist of cell death [KO:K02158]
101274859  CD40LG; CD40 ligand [KO:K03161]
101278975  CD40; tumor necrosis factor receptor superfamily member 5 isoform X2 [KO:K03160]
101270048  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X1 [KO:K09565] [EC:5.2.1.8]
101283796  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
101271889  IL10; interleukin-10 [KO:K05443]
101281088  IL10RA; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
101283710  IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
101278346  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X2 [KO:K11219] [EC:2.7.10.2]
101281369  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
101286197  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
101276254  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
101289027  TGFB3; transforming growth factor beta-3 proprotein [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
oor00590  Arachidonic acid metabolism
oor04010  MAPK signaling pathway
oor04144  Endocytosis
oor04210  Apoptosis
oor04620  Toll-like receptor signaling pathway
oor04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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