KEGG   PATHWAY: panu05145
Entry
panu05145                   Pathway                                
Name
Toxoplasmosis - Papio anubis (olive baboon)
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
panu05145  Toxoplasmosis
panu05145

Organism
Papio anubis (olive baboon) [GN:panu]
Gene
100126724  IFNG; interferon gamma precursor [KO:K04687]
101000704  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
100137246  IFNGR2; interferon gamma receptor 2 precursor [KO:K05133]
101002872  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
101007171  JAK2; tyrosine-protein kinase JAK2 isoform X4 [KO:K04447] [EC:2.7.10.2]
101005886  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101006064  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
110743061  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
103883612  HLA class II histocompatibility antigen, DM alpha chain isoform X2 [KO:K06752]
101016766  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
101017941  HLA class II histocompatibility antigen, DO alpha chain isoform X7 [KO:K06752]
101014430  HLA class II histocompatibility antigen, DRB1-15 beta chain isoform X1 [KO:K06752]
116268485  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
101018551  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
101000981  HLA class II histocompatibility antigen, DP beta 1 chain-like precursor [KO:K06752]
101018895  HLA class II histocompatibility antigen, DP alpha 1 chain precursor [KO:K06752]
101019718  nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
101008144  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
101005327  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
101018336  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
101007351  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101002649  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101013055  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101011339  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
100997900  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
101012041  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101006756  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101005010  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
101022320  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101019884  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101012583  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
101001515  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X4 [KO:K04433] [EC:2.7.12.2]
101001103  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
101002393  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101024189  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101024771  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100998877  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101016447  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X5 [KO:K07209] [EC:2.7.11.10]
101023751  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100998839  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
101026781  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X6 [KO:K02580]
101017078  RELA; transcription factor p65 isoform X1 [KO:K04735]
100126719  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
100126717  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
101026183  BCL2; apoptosis regulator Bcl-2 isoform X3 [KO:K02161]
101019436  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101026503  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060]
100997299  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100998457  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 8 [KO:K04725] [EC:2.3.2.27]
101022825  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
101016461  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
101026000  LY96; lymphocyte antigen 96 isoform X3 [KO:K05400]
101009041  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
101009582  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
101024987  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
103884712  TLR2; toll-like receptor 2 [KO:K10159]
101009064  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
101005361  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
116272742  laminin subunit alpha-1-like isoform X1 [KO:K05637]
101024356  LAMA5; laminin subunit alpha-5 [KO:K06240]
101009063  LAMA3; laminin subunit alpha-3 isoform X5 [KO:K06240]
101002096  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
101025814  LAMB1; LOW QUALITY PROTEIN: laminin subunit beta-1 [KO:K05636]
101000787  LAMB2; laminin subunit beta-2 [KO:K06243]
101005084  LAMB3; laminin subunit beta-3 isoform X1 [KO:K06244]
101026514  LAMB4; laminin subunit beta-4 [KO:K06245]
101008905  LAMC1; laminin subunit gamma-1 isoform X1 [KO:K05635]
101007972  LAMC2; laminin subunit gamma-2 [KO:K06246]
101006376  LAMC3; laminin subunit gamma-3 [KO:K06247]
100999739  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
101005052  ITGB1; integrin beta-1 isoform X2 [KO:K05719]
101016912  LDLR; low-density lipoprotein receptor [KO:K12473]
101013835  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101009470  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101023728  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
101025906  cytochrome c-like [KO:K08738]
101020480  cytochrome c-like [KO:K08738]
101021327  cytochrome c-like [KO:K08738]
101014039  cytochrome c-like [KO:K08738]
101008579  cytochrome c [KO:K08738]
100997529  cytochrome c [KO:K08738]
101021349  cytochrome c-like [KO:K08738]
100997503  cytochrome c-like [KO:K08738]
101019410  cytochrome c-like [KO:K08738]
103878393  cytochrome c-like [KO:K08738]
108582823  cytochrome c-like [KO:K08738]
101014473  cytochrome c-like [KO:K08738]
101009907  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
101011013  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101011251  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101020528  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
101018328  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
101018542  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
101000692  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
101001384  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101006436  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100997634  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101000402  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100381179  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101012551  BAD; bcl2-associated agonist of cell death [KO:K02158]
101011100  CD40LG; CD40 ligand [KO:K03161]
101002143  CD40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
100997257  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
100126710  CCR5; C-C chemokine receptor type 5 [KO:K04180]
101004229  ALOX5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
101024270  IL10; interleukin-10 [KO:K05443]
101014353  IL10RA; interleukin-10 receptor subunit alpha isoform X2 [KO:K05134]
100137244  IL10RB; interleukin-10 receptor subunit beta precursor [KO:K05135]
101020681  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
100998929  STAT3; signal transducer and activator of transcription 3 isoform X9 [KO:K04692]
101006627  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
101009253  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100997116  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
panu00590  Arachidonic acid metabolism
panu04010  MAPK signaling pathway
panu04144  Endocytosis
panu04210  Apoptosis
panu04620  Toll-like receptor signaling pathway
panu04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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