KEGG   PATHWAY: npo05145
Entry
npo05145                    Pathway                                
Name
Toxoplasmosis - Nyctereutes procyonoides (raccoon dog)
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
npo05145  Toxoplasmosis
npo05145

Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129512215  IFNG; interferon gamma [KO:K04687]
129509273  IFNGR1; interferon gamma receptor 1 [KO:K05132]
129502066  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
129497055  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
129499911  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
129522804  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
129520130  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
129512314  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
129512546  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
129512547  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
129512797  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
129512799  LOW QUALITY PROTEIN: RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
129513026  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
129513027  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
129513028  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129513030  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
129495012  immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
129495019  immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
129515870  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
129519759  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
129506934  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
129518585  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
129505651  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
129494142  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
129512811  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
129511324  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
129499952  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
129502349  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
129507918  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129519082  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129494670  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
129501796  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
129522825  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
129497110  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
129508745  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
129511619  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
129511620  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
129512956  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
129512957  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
129493669  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129515857  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
129517602  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
129499457  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129499646  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
129521190  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129503049  RELA; transcription factor p65 isoform X1 [KO:K04735]
129498700  IL12A; interleukin-12 subunit alpha isoform X1 [KO:K05406]
129509743  IL12B; interleukin-12 subunit beta [KO:K05425]
129512779  TNF; tumor necrosis factor [KO:K03156]
129495480  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129514527  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129496481  BCL2L1; bcl-2-like protein 1 [KO:K04570]
129497162  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
129497816  baculoviral IAP repeat-containing protein 3 [KO:K16060]
129517703  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
129496284  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
129505396  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
129494517  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
129503012  heat shock cognate 71 kDa protein [KO:K03283]
129496819  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
129512479  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
129512480  heat shock 70 kDa protein 1 [KO:K03283]
129512788  heat shock 70 kDa protein 1 [KO:K03283]
129514743  heat shock cognate 71 kDa protein-like [KO:K03283]
129516767  TLR2; toll-like receptor 2 [KO:K10159]
129509151  LAMA1; laminin subunit alpha-1 [KO:K05637]
129499887  LAMA2; laminin subunit alpha-2 [KO:K05637]
129508841  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
129496449  LAMA5; laminin subunit alpha-5 [KO:K06240]
129512475  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
129494237  LAMB1; laminin subunit beta-1 [KO:K05636]
129521921  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
129505974  LAMB3; laminin subunit beta-3 [KO:K06244]
129494236  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
129505908  LAMC1; laminin subunit gamma-1 [KO:K05635]
129505982  LAMC2; laminin subunit gamma-2 [KO:K06246]
129510461  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
129498507  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
129499050  ITGB1; integrin beta-1 [KO:K05719]
129521725  LDLR; low-density lipoprotein receptor [KO:K12473]
129503428  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
129523021  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
129503548  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
129502969  cytochrome c [KO:K08738]
129506647  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
129515281  cytochrome c-like [KO:K08738]
129518214  cytochrome c-like [KO:K08738]
129513406  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129494269  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129519569  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
129522106  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
129513852  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
129494039  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
129496567  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
129497926  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
129519211  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
129508823  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129495892  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129499851  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129517633  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129514778  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129503119  BAD; bcl2-associated agonist of cell death [KO:K02158]
129518821  CD40LG; CD40 ligand [KO:K03161]
129521609  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
129509841  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
129521913  CCR5; C-C chemokine receptor type 5 isoform X1 [KO:K04180]
129522715  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
129505964  IL10; interleukin-10 [KO:K05443]
129497014  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
129502076  IL10RB; interleukin-10 receptor subunit beta [KO:K05135]
129521932  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
129506479  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
129500810  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
129515208  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
129496088  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
npo00590  Arachidonic acid metabolism
npo04010  MAPK signaling pathway
npo04144  Endocytosis
npo04210  Apoptosis
npo04620  Toll-like receptor signaling pathway
npo04630  JAK-STAT signaling pathway
KO pathway
ko05145   
LinkDB

DBGET integrated database retrieval system