KEGG   PATHWAY: phas05145
Entry
phas05145                   Pathway                                
Name
Toxoplasmosis - Phyllostomus hastatus (greater spear-nosed bat)
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
phas05145  Toxoplasmosis
phas05145

Organism
Phyllostomus hastatus (greater spear-nosed bat) [GN:phas]
Gene
123812973  IFNG; interferon gamma [KO:K04687]
123821790  IFNGR1; interferon gamma receptor 1 [KO:K05132]
123828042  IFNGR2; interferon gamma receptor 2 [KO:K05133]
123816436  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
123819931  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
123816523  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
123806498  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
123815923  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
123816020  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
123816129  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
123816250  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
123816448  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
123810280  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
123810358  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
123817124  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
123806422  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
123808475  toll-like receptor 11 isoform X1 [KO:K14142]
123830839  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
123823090  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
123812800  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
123809979  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
123821751  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
123816012  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
123821688  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
123806569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123825523  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123820887  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123806902  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807193  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123809430  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
123817154  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
123822258  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123822259  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123816206  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123816247  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123828668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
123807522  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
123823081  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
123825207  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123823806  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
123806785  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123829518  RELA; transcription factor p65 [KO:K04735]
123827188  IL12A; interleukin-12 subunit alpha [KO:K05406]
123811597  IL12B; interleukin-12 subunit beta [KO:K05425]
123810433  TNF; tumor necrosis factor isoform X1 [KO:K03156]
123826047  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123814855  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
123805465  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
123805489  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
123827723  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
123814966  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
123825803  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
123820226  TLR4; toll-like receptor 4 [KO:K10160]
123810362  heat shock 70 kDa protein 1 [KO:K03283]
123810504  heat shock 70 kDa protein 1-like [KO:K03283]
123832579  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
123813727  TLR2; toll-like receptor 2 [KO:K10159]
123826329  LAMA1; laminin subunit alpha-1 [KO:K05637]
123821337  LAMA2; laminin subunit alpha-2 isoform X1 [KO:K05637]
123826058  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
123814754  LAMA5; laminin subunit alpha-5 [KO:K06240]
123821757  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
123811425  LAMB1; laminin subunit beta-1 [KO:K05636]
123830578  laminin subunit beta-2 [KO:K06243]
123830721  laminin subunit beta-2-like [KO:K06243]
123818499  LAMB3; laminin subunit beta-3 [KO:K06244]
123811550  LAMB4; laminin subunit beta-4 [KO:K06245]
123818340  LAMC1; laminin subunit gamma-1 [KO:K05635]
123818501  LAMC2; laminin subunit gamma-2 [KO:K06246]
123823475  LAMC3; laminin subunit gamma-3 [KO:K06247]
123824106  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
123806803  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
123828240  LDLR; low-density lipoprotein receptor [KO:K12473]
123810612  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
123824482  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
123807416  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
123811546  cytochrome c [KO:K08738]
123811721  cytochrome c-like [KO:K08738]
123826376  cytochrome c-like [KO:K08738]
123826264  cytochrome c-like [KO:K08738]
123832288  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
123804401  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123811789  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123830671  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123805731  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
123811696  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
123809306  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
123809423  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
123807097  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
123808608  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123823743  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123832297  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123829336  BAD; bcl2-associated agonist of cell death [KO:K02158]
123819099  CD40LG; CD40 ligand [KO:K03161]
123814884  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
123821079  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
123830646  CCR5; C-C chemokine receptor type 5 [KO:K04180]
123821021  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
123820638  IL10; interleukin-10 [KO:K05443]
123818932  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
123827994  IL10RB; interleukin-10 receptor subunit beta [KO:K05135]
123828369  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
123816770  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
123823713  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
123804941  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
123808879  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
phas00590  Arachidonic acid metabolism
phas04010  MAPK signaling pathway
phas04144  Endocytosis
phas04210  Apoptosis
phas04620  Toll-like receptor signaling pathway
phas04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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