KEGG   PATHWAY: mcf05145
Entry
mcf05145                    Pathway                                
Name
Toxoplasmosis - Macaca fascicularis (crab-eating macaque)
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
mcf05145  Toxoplasmosis
mcf05145

Organism
Macaca fascicularis (crab-eating macaque) [GN:mcf]
Gene
102128291  IFNG; interferon gamma [KO:K04687]
101866179  IFNGR1; interferon gamma receptor 1 isoform X3 [KO:K05132]
102138221  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102123983  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102119008  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
101925134  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
102129555  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
102136468  HLA class II histocompatibility antigen, DP beta 1 chain isoform X1 [KO:K06752]
102137481  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
102140649  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
102139994  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
102145413  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
102132662  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102144414  HLA class II histocompatibility antigen, DR beta 5 chain isoform X1 [KO:K06752]
102144039  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
102136862  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
102133044  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752]
123572852  H-2 class II histocompatibility antigen, A-D alpha chain-like [KO:K06752]
123572854  class II histocompatibility antigen, B-L beta chain-like [KO:K06752]
123572909  mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
102121432  NOS2; LOW QUALITY PROTEIN: nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
102135411  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
101866832  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
102134829  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
102140231  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102128596  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102140498  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102122493  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
101865975  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102145011  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102116996  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
102118497  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126339  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102121272  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102116823  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
101925060  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X3 [KO:K04433] [EC:2.7.12.2]
101867352  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
101926770  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102134421  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101867305  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102115964  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102146604  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
102115368  IKBKG; NF-kappa-B essential modulator isoform X5 [KO:K07210]
101867458  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102130059  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
102138273  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101867324  RELA; transcription factor p65 isoform X1 [KO:K04735]
102115316  IL12A; interleukin-12 subunit alpha [KO:K05406]
102124858  IL12B; interleukin-12 subunit beta [KO:K05425]
102139631  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102138212  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
102140222  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
102137780  baculoviral IAP repeat-containing protein 3 [KO:K16060]
102138168  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
102131393  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
102126399  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 8 [KO:K04725] [EC:2.3.2.27]
102121739  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X2 [KO:K16061]
102118398  LY96; lymphocyte antigen 96 isoform X2 [KO:K05400]
102136906  TLR4; toll-like receptor 4 isoform X2 [KO:K10160]
102143176  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
102129925  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
101925240  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
102131294  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
101926012  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
123572795  heat shock 70 kDa protein 1A [KO:K03283]
102146068  TLR2; toll-like receptor 2 [KO:K10159]
102145776  LAMA2; laminin subunit alpha-2 isoform X6 [KO:K05637]
102146003  LAMA1; laminin subunit alpha-1 isoform X2 [KO:K05637]
102128796  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
102120952  LAMA3; laminin subunit alpha-3 isoform X2 [KO:K06240]
102132640  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
102126233  LAMB1; laminin subunit beta-1 [KO:K05636]
102135628  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
102116149  LAMB3; laminin subunit beta-3 [KO:K06244]
102126627  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
102116045  LAMC1; laminin subunit gamma-1 [KO:K05635]
102116676  LAMC2; laminin subunit gamma-2 [KO:K06246]
102147194  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
101925271  ITGA6; integrin alpha-6 isoform X3 [KO:K06485]
102144610  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
102127361  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
102135285  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101865354  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
102144182  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
102117102  cytochrome c-like [KO:K08738]
102120205  cytochrome c [KO:K08738]
102125088  cytochrome c-like [KO:K08738]
102136392  cytochrome c-like [KO:K08738]
102127614  cytochrome c-like [KO:K08738]
102141866  cytochrome c-like [KO:K08738]
107127908  cytochrome c-like [KO:K08738]
102120841  cytochrome c-like [KO:K08738]
102123704  cytochrome c-like [KO:K08738]
107130218  cytochrome c-like [KO:K08738]
102126830  CASP9; LOW QUALITY PROTEIN: caspase-9 [KO:K04399] [EC:3.4.22.62]
102119905  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 isoform X1 [KO:K04630]
102140224  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
101926144  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
102131761  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
102146644  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
102135867  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
102133347  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
101866379  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102144461  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102142406  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102132744  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102121921  BAD; bcl2-associated agonist of cell death [KO:K02158]
102138630  CD40LG; CD40 ligand [KO:K03161]
102118696  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
102124789  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X2 [KO:K09565] [EC:5.2.1.8]
102139456  CCR5; C-C chemokine receptor type 5 [KO:K04180]
102132853  ALOX5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
102133450  IL10; interleukin-10 [KO:K05443]
102127536  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
102139461  IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
102143094  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102118402  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
102129546  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
101925182  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
102119907  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
mcf00590  Arachidonic acid metabolism
mcf04010  MAPK signaling pathway
mcf04144  Endocytosis
mcf04210  Apoptosis
mcf04620  Toll-like receptor signaling pathway
mcf04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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