KEGG   PATHWAY: aml05145
Entry
aml05145                    Pathway                                
Name
Toxoplasmosis - Ailuropoda melanoleuca (giant panda)
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
aml05145  Toxoplasmosis
aml05145

Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100462659  IFNG; interferon gamma precursor [KO:K04687]
100473768  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100481672  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
100473460  JAK1; tyrosine-protein kinase JAK1 isoform X2 [KO:K11217] [EC:2.7.10.2]
100481360  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
100474026  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100480688  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
100464393  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100464636  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
100477284  HLA class II histocompatibility antigen, DM beta chain isoform X2 [KO:K06752]
100478290  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
100484974  HLA class II histocompatibility antigen, DQ beta 2 chain [KO:K06752]
100464780  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
100464279  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
100478546  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
100463634  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
100464025  LOW QUALITY PROTEIN: SLA class II histocompatibility antigen, DQ haplotype C alpha chain [KO:K06752]
100464289  immunity-related GTPase family M protein 1 isoform X1 [KO:K14139] [EC:3.6.5.-]
100463703  immunity-related GTPase family M protein 1-like isoform X1 [KO:K14139] [EC:3.6.5.-]
117801422  LOW QUALITY PROTEIN: immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
100470060  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
100480183  SOCS1; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1 [KO:K04694]
100479307  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
100484977  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
100469127  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
100483216  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100466506  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100484077  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403]
100468085  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100477951  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100482196  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100477600  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
100476678  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
100469111  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
100465223  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100465476  MAPK14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
100480235  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100480483  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100464675  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100471679  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100470223  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100466997  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100466767  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
100467906  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100480158  RELA; transcription factor p65 isoform X1 [KO:K04735]
100470471  IL12A; interleukin-12 subunit alpha isoform X2 [KO:K05406]
100477772  IL12B; interleukin-12 subunit beta [KO:K05425]
100471563  TNF; tumor necrosis factor [KO:K03156]
100484344  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
100469922  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100477152  baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100477406  baculoviral IAP repeat-containing protein 2 [KO:K16060]
100471203  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100483031  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
100468714  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
100472815  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
100468647  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
100483310  heat shock 70 kDa protein 1-like [KO:K03283]
100483558  heat shock 70 kDa protein 1 [KO:K03283]
100469467  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
117800506  heat shock cognate 71 kDa protein-like isoform X1 [KO:K03283]
100465129  TLR2; toll-like receptor 2 [KO:K10159]
100484712  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
100465830  LAMA1; laminin subunit alpha-1 [KO:K05637]
100484669  LAMA3; laminin subunit alpha-3 isoform X3 [KO:K06240]
100482780  LAMA5; laminin subunit alpha-5 [KO:K06240]
100472419  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
100472572  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
100477974  LAMB2; laminin subunit beta-2 [KO:K06243]
100465597  LAMB3; laminin subunit beta-3 isoform X2 [KO:K06244]
100477380  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
100476326  LAMC1; laminin subunit gamma-1 [KO:K05635]
100475077  LAMC2; laminin subunit gamma-2 [KO:K06246]
100477198  LAMC3; laminin subunit gamma-3 [KO:K06247]
100474079  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100482697  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100473450  LDLR; low-density lipoprotein receptor isoform X2 [KO:K12473]
100479926  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100472842  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
100469056  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
100472074  cytochrome c [KO:K08738]
105241648  cytochrome c-like [KO:K08738]
100483760  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100471767  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100484933  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100466408  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100466130  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
100470322  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X2 [KO:K21289] [EC:2.7.1.153]
100477067  PIK3R5; LOW QUALITY PROTEIN: phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
100477324  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
100473305  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100473937  BAD; bcl2-associated agonist of cell death [KO:K02158]
100467917  CD40LG; CD40 ligand [KO:K03161]
100476345  CD40; tumor necrosis factor receptor superfamily member 5 isoform X2 [KO:K03160]
100481603  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
100465045  C-C chemokine receptor type 5 [KO:K04180]
100476416  ALOX5; arachidonate 5-lipoxygenase isoform X2 [KO:K00461] [EC:1.13.11.34]
100481671  IL10; interleukin-10 [KO:K05443]
100469546  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
109488333  IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
100468422  TYK2; LOW QUALITY PROTEIN: non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100469938  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
100470703  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
100463584  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100475861  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [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
aml00590  Arachidonic acid metabolism
aml04010  MAPK signaling pathway
aml04144  Endocytosis
aml04210  Apoptosis
aml04620  Toll-like receptor signaling pathway
aml04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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