KEGG   PATHWAY: mlk05145
Entry
mlk05145                    Pathway                                
Name
Toxoplasmosis - Mustela lutreola (European mink)
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
mlk05145  Toxoplasmosis
mlk05145

Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131839127  IFNG; interferon gamma [KO:K04687]
131833755  IFNGR1; interferon gamma receptor 1 [KO:K05132]
131825325  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
131809752  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
131813137  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
131827656  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
131819154  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
131834264  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
131834265  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
131834269  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
131834270  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
131834274  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
131834279  HLA class II histocompatibility antigen, DQ beta 2 chain-like isoform X1 [KO:K06752]
131834280  HLA class II histocompatibility antigen, DQ beta 1 chain-like isoform X1 [KO:K06752]
131834281  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
131834282  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
131834285  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
131834286  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
131834287  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
131830546  LOW QUALITY PROTEIN: SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
131833234  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
131832671  immunity-related GTPase family M protein 1-like isoform X1 [KO:K14139] [EC:3.6.5.-]
131832676  immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
131816344  NOS2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:1.14.13.39]
131819736  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
131824370  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
131820794  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
131838863  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
131811444  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
131833596  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
131839494  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
131833695  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
131811758  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
131820131  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
131828723  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
131831160  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
131832665  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
131816095  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
131816040  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
131839655  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
131839656  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
131834189  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
131834191  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
131828549  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
131820342  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
131822182  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
131836470  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
131817751  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
131829855  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
131815578  RELA; transcription factor p65 [KO:K04735]
131824928  IL12A; interleukin-12 subunit alpha [KO:K05406]
131831849  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
131834372  TNF; tumor necrosis factor isoform X1 [KO:K03156]
131811845  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
131807889  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
131834540  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
131834551  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
131822235  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
131807312  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
131826700  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
131812598  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
131837691  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
131833881  heat shock cognate 71 kDa protein-like [KO:K03283]
131834338  heat shock 70 kDa protein 1-like [KO:K03283]
131834339  heat shock 70 kDa protein 1 [KO:K03283]
131834340  heat shock 70 kDa protein 1-like [KO:K03283]
131832001  heat shock cognate 71 kDa protein-like [KO:K03283]
131831467  TLR2; toll-like receptor 2 [KO:K10159]
131833812  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
131811428  LAMA1; laminin subunit alpha-1 [KO:K05637]
131811666  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
131808591  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
131833489  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
131829232  LAMB1; laminin subunit beta-1 [KO:K05636]
131823907  LAMB2; laminin subunit beta-2 [KO:K06243]
131815308  LAMB3; laminin subunit beta-3 [KO:K06244]
131829234  LAMB4; laminin subunit beta-4 [KO:K06245]
131815290  LAMC1; laminin subunit gamma-1 [KO:K05635]
131814364  LAMC2; laminin subunit gamma-2 [KO:K06246]
131812737  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
131827091  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
131838306  ITGB1; integrin beta-1 [KO:K05719]
131823540  LDLR; low-density lipoprotein receptor [KO:K12473]
131838434  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
131827572  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
131820467  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
131833963  cytochrome c-like [KO:K08738]
131834139  cytochrome c [KO:K08738]
131829521  cytochrome c [KO:K08738]
131809520  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
131829305  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
131823969  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
131810079  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
131818465  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
131829247  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
131815847  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
131816268  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
131819765  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
131837056  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
131815063  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131817507  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131814653  BAD; bcl2-associated agonist of cell death [KO:K02158]
131821750  CD40LG; CD40 ligand [KO:K03161]
131807685  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
131828775  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X1 [KO:K09565] [EC:5.2.1.8]
131823851  C-C chemokine receptor type 5 [KO:K04180]
131828702  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
131815004  IL10; interleukin-10 [KO:K05443]
131836510  IL10RA; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
131823516  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
131816590  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
131817494  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
131815106  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
131836852  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
mlk00590  Arachidonic acid metabolism
mlk04010  MAPK signaling pathway
mlk04144  Endocytosis
mlk04210  Apoptosis
mlk04620  Toll-like receptor signaling pathway
mlk04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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