KEGG   PATHWAY: fca05145
Entry
fca05145                    Pathway                                
Name
Toxoplasmosis - Felis catus (domestic cat)
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
fca05145  Toxoplasmosis
fca05145

Organism
Felis catus (domestic cat) [GN:fca]
Gene
493965  IFNG; interferon gamma precursor [KO:K04687]
101086811  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101092286  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
101084377  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101088959  JAK2; tyrosine-protein kinase JAK2 isoform X2 [KO:K04447] [EC:2.7.10.2]
101084561  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101087372  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
101088996  DRA; HLA class II histocompatibility antigen, DR alpha chain-like precursor [KO:K06752]
100169654  SLC26A3; chloride anion exchanger precursor [KO:K06752]
101098301  DLA class II histocompatibility antigen, DR-1 beta chain precursor [KO:K06752]
111556169  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101082906  HLA class II histocompatibility antigen, DO beta chain isoform X2 [KO:K06752]
101084108  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
101088734  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
111556173  HLA class II histocompatibility antigen, DM beta chain-like isoform X1 [KO:K06752]
101090518  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
111560441  HLA class II histocompatibility antigen, DO beta chain-like isoform X1 [KO:K06752]
101090771  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
111560440  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101082653  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
101090265  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
101084962  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
111560443  HLA class II histocompatibility antigen, DM alpha chain-like [KO:K06752]
111560444  HLA class II histocompatibility antigen, DO alpha chain-like [KO:K06752]
111560445  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752]
111556176  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
111558969  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111558970  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
102899262  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101087020  NOS2; nitric oxide synthase, inducible isoform X2 [KO:K13241] [EC:1.14.13.39]
111558242  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
101087092  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
101090500  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
101100225  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101099750  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101095899  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101083606  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403]
101098714  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101082274  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
101089813  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101095617  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
101086544  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101090622  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101099259  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
100142683  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101096604  RELA; transcription factor p65 [KO:K04735]
493741  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
768273  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493934  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
493701  BCL2L1; bcl-2-like protein 1 [KO:K04570]
101083444  baculoviral IAP repeat-containing protein 3 [KO:K16060]
101101663  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101090594  XIAP; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
101080371  BIRC7; baculoviral IAP repeat-containing protein 7 isoform X1 [KO:K16061]
101100862  LY96; lymphocyte antigen 96 [KO:K05400]
493698  TLR4; toll-like receptor 4 precursor [KO:K10160]
101091022  heat shock 70 kDa protein 1-like [KO:K03283]
101088003  HSPA2; heat shock-related 70 kDa protein 2 [KO:K03283]
101087422  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
493797  TLR2; toll-like receptor 2 [KO:K10159]
101083299  LAMA1; laminin subunit alpha-1 isoform X2 [KO:K05637]
101092612  LAMA2; LOW QUALITY PROTEIN: laminin subunit alpha-2 [KO:K05637]
101100161  LAMA3; laminin subunit alpha-3 isoform X5 [KO:K06240]
101083923  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
101086907  LAMA4; laminin subunit alpha-4 isoform X2 [KO:K06241]
101080367  LAMB1; laminin subunit beta-1 [KO:K05636]
101082047  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
101088641  LAMB3; laminin subunit beta-3 [KO:K06244]
101101552  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
101090321  LAMC1; laminin subunit gamma-1 [KO:K05635]
101089571  LAMC2; laminin subunit gamma-2 [KO:K06246]
101098499  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
101092454  ITGA6; LOW QUALITY PROTEIN: integrin alpha-6 [KO:K06485]
751821  ITGB1; integrin beta-1 precursor [KO:K05719]
101080362  LDLR; low-density lipoprotein receptor isoform X1 [KO:K12473]
493957  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
100142684  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
493932  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
101098213  cytochrome c [KO:K08738]
101094614  cytochrome c, testis-specific-like [KO:K08738]
101088122  cytochrome c-like [KO:K08738]
101100947  cytochrome c [KO:K08738]
768260  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
101092837  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
101100320  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101089679  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101101353  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
101096215  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
101082354  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101082104  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
101101686  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X2 [KO:K06276] [EC:2.7.11.1]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
768269  BAD; bcl2-associated agonist of cell death [KO:K02158]
493850  CD40LG; CD40 ligand [KO:K03161]
101085363  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
101099589  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X5 [KO:K09565] [EC:5.2.1.8]
493769  CCR5; C-C chemokine receptor type 5 [KO:K04180]
101097422  ALOX5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
493683  IL10; interleukin-10 precursor [KO:K05443]
101087601  IL10RA; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
101090038  IL10RB; interleukin-10 receptor subunit beta [KO:K05135]
101090171  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
101095698  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
768263  TGFB1; transforming growth factor beta-1 isoform X2 [KO:K13375]
101093414  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
101098469  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
Compound
C00076  Calcium cation
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06314  Lipoxin A4
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
fca00590  Arachidonic acid metabolism
fca04010  MAPK signaling pathway
fca04144  Endocytosis
fca04210  Apoptosis
fca04620  Toll-like receptor signaling pathway
fca04630  JAK-STAT signaling pathway
KO pathway
ko05145   
LinkDB

DBGET integrated database retrieval system