KEGG   PATHWAY: ray05145
Entry
ray05145                    Pathway                                
Name
Toxoplasmosis - Rousettus aegyptiacus (Egyptian rousette)
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
ray05145  Toxoplasmosis
ray05145

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107512682  IFNG; interferon gamma [KO:K04687]
107521298  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
107519538  IFNGR2; interferon gamma receptor 2 [KO:K05133]
107517940  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
107507294  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
107519182  STAT1; LOW QUALITY PROTEIN: signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
107518200  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
107506765  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
107506766  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
107505772  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107505773  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
107505774  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107511941  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
107511990  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
107511992  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
107511993  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
107511999  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
107512001  HLA class II histocompatibility antigen, DQ beta 1 chain-like isoform X1 [KO:K06752]
107507331  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107507332  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like isoform X1 [KO:K06752]
107497410  NOS2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:1.14.13.39]
107518217  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
107499600  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
107517734  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
107511752  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
107499247  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
107508648  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
107500809  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
107518453  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107512328  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107509910  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107515392  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107506757  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
107510279  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
107497883  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107497895  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107500264  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
107500274  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107499756  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
107501353  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
107499585  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
107514416  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
107520958  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
107517900  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107497522  RELA; transcription factor p65 [KO:K04735]
107512954  IL12A; interleukin-12 subunit alpha [KO:K05406]
107521891  IL12B; interleukin-12 subunit beta [KO:K05425]
107498497  TNF; tumor necrosis factor [KO:K03156]
107503915  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
107512887  BCL2L1; bcl-2-like protein 1 [KO:K04570]
107504640  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
107504641  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
107497750  XIAP; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
107505775  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
107515178  LY96; lymphocyte antigen 96 [KO:K05400]
107514466  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
107503644  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
107498470  LOW QUALITY PROTEIN: heat shock 70 kDa protein 1-like [KO:K03283]
107498471  heat shock 70 kDa protein 1-like isoform X1 [KO:K03283]
107498469  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
107510758  TLR2; toll-like receptor 2 isoform X1 [KO:K10159]
107497012  LAMA2; laminin subunit alpha-2 [KO:K05637]
107498184  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
107503661  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
107521547  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
107506303  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
107501076  LAMB1; laminin subunit beta-1 [KO:K05636]
107513328  LAMB2; laminin subunit beta-2 isoform X1 [KO:K06243]
107517630  LAMB3; laminin subunit beta-3 [KO:K06244]
107501119  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
107511293  LAMC1; laminin subunit gamma-1 [KO:K05635]
107511295  LAMC2; laminin subunit gamma-2 [KO:K06246]
107504553  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
107505202  integrin alpha-6 isoform X1 [KO:K06485]
107499295  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
107515081  LDLR; low-density lipoprotein receptor [KO:K12473]
107519788  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
107503155  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
107510456  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
107518128  cytochrome c [KO:K08738]
107501830  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
107516134  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107518173  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107513376  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107499654  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
107511488  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
107515658  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
107515659  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
107498762  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107497091  BAD; bcl2-associated agonist of cell death [KO:K02158]
107501399  CD40LG; CD40 ligand [KO:K03161]
107514532  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
107520810  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
107509099  C-C chemokine receptor type 5-like [KO:K04180]
107508911  ALOX5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
107502233  IL10; interleukin-10 [KO:K05443]
107516126  IL10RA; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
107519579  IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
107515075  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
107513823  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
107505490  TGFB1; transforming growth factor beta-1 [KO:K13375]
107520844  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
107498899  TGFB3; transforming growth factor beta-3 [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
ray00590  Arachidonic acid metabolism
ray04010  MAPK signaling pathway
ray04144  Endocytosis
ray04210  Apoptosis
ray04620  Toll-like receptor signaling pathway
ray04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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