KEGG   PATHWAY: maua05145
Entry
maua05145                   Pathway                                
Name
Toxoplasmosis - Mesocricetus auratus (golden hamster)
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
maua05145  Toxoplasmosis
maua05145

Organism
Mesocricetus auratus (golden hamster) [GN:maua]
Gene
101825431  Ifng; interferon gamma precursor [KO:K04687]
101827289  Ifngr1; interferon gamma receptor 1 [KO:K05132]
101828108  Ifngr2; interferon gamma receptor 2 isoform X1 [KO:K05133]
101843653  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101831977  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101827798  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101825611  Ciita; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
110339871  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
110339725  H-2 class II histocompatibility antigen, E-D beta chain-like [KO:K06752]
101833734  H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
101829780  H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
101844521  class II histocompatibility antigen, M beta 1 chain [KO:K06752]
101834602  H-2 class II histocompatibility antigen, A-U alpha chain [KO:K06752]
101834868  rano class II histocompatibility antigen, A beta chain [KO:K06752]
101822444  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
101822719  HLA class II histocompatibility antigen, DP beta 1 chain isoform X1 [KO:K06752]
101828355  H-2 class II histocompatibility antigen, E-U alpha chain [KO:K06752]
101844256  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
101844787  class II histocompatibility antigen, M alpha chain [KO:K06752]
101837127  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
101843733  H-2 class II histocompatibility antigen, E-D beta chain-like [KO:K06752]
101839900  LOW QUALITY PROTEIN: immunity-related GTPase family M protein 1 [KO:K14139] [EC:3.6.5.-]
121141307  LOW QUALITY PROTEIN: immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
101837226  immunity-related GTPase family M protein 1 isoform X3 [KO:K14140]
101823656  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
101827454  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
101840985  toll-like receptor 11 [KO:K14142]
101828578  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
101830300  Irak1; interleukin-1 receptor-associated kinase 1 isoform X4 [KO:K04730] [EC:2.7.11.1]
101824326  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
101830563  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101822685  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101832517  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
101844616  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
101825943  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101841668  Mapk3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101832187  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101827071  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101841730  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101838194  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
101833237  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101824303  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101824910  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101826592  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101833914  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101837015  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101834429  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
101824046  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101835014  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
101831453  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
101839499  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101831177  Rela; transcription factor p65 isoform X1 [KO:K04735]
101844248  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
101843678  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
101843732  Tnf; tumor necrosis factor [KO:K03156]
101833785  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
101834682  Bcl2l1; bcl-2-like protein 1 [KO:K04570]
110339912  baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
101835694  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101824803  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
101822848  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
101836262  Ly96; LOW QUALITY PROTEIN: lymphocyte antigen 96 [KO:K05400]
101824088  Tlr4; toll-like receptor 4 [KO:K10160]
121134227  heat shock 70 kDa protein 1A [KO:K03283]
101828609  heat shock 70 kDa protein 1-like [KO:K03283]
101830239  heat shock 70 kDa protein 1A [KO:K03283]
101844643  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
121140148  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
101838156  Tlr2; toll-like receptor 2 isoform X1 [KO:K10159]
101822630  Lama2; laminin subunit alpha-2 isoform X1 [KO:K05637]
101824731  Lama1; laminin subunit alpha-1 [KO:K05637]
101837968  Lama5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
101839171  Lama3; laminin subunit alpha-3 isoform X1 [KO:K06240]
101834813  Lama4; laminin subunit alpha-4 [KO:K06241]
101830978  Lamb1; laminin subunit beta-1 [KO:K05636]
101842429  Lamb2; laminin subunit beta-2 isoform X1 [KO:K06243]
101834766  Lamb3; laminin subunit beta-3 [KO:K06244]
101830595  Lamc1; laminin subunit gamma-1 [KO:K05635]
101824254  Lamc2; laminin subunit gamma-2 isoform X2 [KO:K06246]
121136460  laminin subunit gamma-3-like [KO:K06247]
121137946  LOW QUALITY PROTEIN: laminin subunit gamma-3-like [KO:K06247]
121138416  LOW QUALITY PROTEIN: laminin subunit gamma-3-like [KO:K06247]
101839961  Itga6; integrin alpha-6 isoform X1 [KO:K06485]
101835360  Itgb1; integrin beta-1 [KO:K05719]
101828208  Ldlr; low-density lipoprotein receptor isoform X1 [KO:K12473]
101840696  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101825474  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101828960  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
106021303  cytochrome c, somatic [KO:K08738]
101842058  cytochrome c, somatic-like [KO:K08738]
110342638  cytochrome c, testis-specific [KO:K08738]
101840173  cytochrome c, somatic-like [KO:K08738]
121136793  cytochrome c, somatic [KO:K08738]
101828663  cytochrome c, somatic-like [KO:K08738]
121140190  cytochrome c, somatic-like [KO:K08738]
101844218  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101832028  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101831676  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101828746  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101830536  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
101833768  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
101844631  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
101844531  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
101835018  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X3 [KO:K06276] [EC:2.7.11.1]
101842312  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101825464  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101840296  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101836153  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
101834854  Cd40lg; CD40 ligand [KO:K03161]
101822705  Cd40; tumor necrosis factor receptor superfamily member 5 isoform X2 [KO:K03160]
101825364  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
101833790  C-C chemokine receptor type 5 [KO:K04180]
101839970  Alox5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
101840942  Il10; interleukin-10 [KO:K05443]
101838397  Il10ra; interleukin-10 receptor subunit alpha [KO:K05134]
101828644  Il10rb; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
101833177  Tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
101834358  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
101834601  Tgfb1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
101832748  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
101840590  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
maua00590  Arachidonic acid metabolism
maua04010  MAPK signaling pathway
maua04144  Endocytosis
maua04210  Apoptosis
maua04620  Toll-like receptor signaling pathway
maua04630  JAK-STAT signaling pathway
KO pathway
ko05145   
LinkDB

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