KEGG   PATHWAY: bta05145
Entry
bta05145                    Pathway                                
Name
Toxoplasmosis - Bos taurus (cow)
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
bta05145  Toxoplasmosis
bta05145

Organism
Bos taurus (cow) [GN:bta]
Gene
281237  IFNG; interferon gamma precursor [KO:K04687]
508619  IFNGR1; interferon gamma receptor 1 precursor [KO:K05132]
514889  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
537201  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
525246  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
510814  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
508720  CIITA; MHC class II transactivator isoform X1 [KO:K08060] [EC:2.7.11.1]
282490  BOLA-DMA; HLA class II histocompatibility antigen, DM alpha chain precursor [KO:K06752]
282491  BOLA-DMB; major histocompatibility complex, class II, DM beta precursor [KO:K06752]
282493  BOLA-DOB; HLA class II histocompatibility antigen, DO beta chain precursor [KO:K06752]
282494  BOLA-DQA5; major histocompatibility complex, class II, DQ alpha 5 precursor [KO:K06752]
282495  BOLA-DQB; major histocompatibility complex, class II, DQ beta precursor [KO:K06752]
282498  BOLA-DYB; major histocompatibility complex, class II, DY beta precursor [KO:K06752]
282535  BOLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
282530  BOLA-DRB3; major histocompatibility complex, class II, DRB3 [KO:K06752]
525727  BOLA-DOA; HLA class II histocompatibility antigen, DO alpha chain precursor [KO:K06752]
506214  BOLA-DRA; major histocompatibility complex, class II, DR alpha precursor [KO:K06752]
539241  BLA-DQB; boLa class II histocompatibility antigen, DQB*0101 beta chain precursor [KO:K06752]
100848815  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like precursor [KO:K06752]
282497  BOLA-DYA; major histocompatibility complex, class II, DY alpha precursor [KO:K06752]
618722  DSB; MHC class II antigen DS beta [KO:K06752]
538700  BOLA-DRB2; HLA class II histocompatibility antigen, DR beta 5 chain isoform X3 [KO:K06752]
282876  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
518795  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
444881  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
533953  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
533692  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
539124  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
782032  LOW QUALITY PROTEIN: TNF receptor-associated factor 6-like [KO:K03175] [EC:2.3.2.27]
529146  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
519958  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
540203  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
539941  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
534125  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
537631  MAPK10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
516039  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
286883  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
534492  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
535327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
512943  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
618906  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
281073  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
281854  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
281855  IKBKG; NF-kappa-B essential modulator [KO:K07210]
282291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
525408  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
616115  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
508233  RELA; transcription factor p65 [KO:K04735]
281856  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
281857  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
280943  TNF; tumor necrosis factor [KO:K03156]
281020  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
282152  BCL2L1; bcl-2-like protein 1 [KO:K04570]
539314  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060]
514386  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
101905053  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2-like [KO:K16060]
281647  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
514508  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
613753  LY96; lymphocyte antigen 96 precursor [KO:K05400]
281536  TLR4; toll-like receptor 4 precursor [KO:K10160]
282254  HSPA1A; heat shock 70 kDa protein 1B [KO:K03283]
281831  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
540190  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
539835  HSPA6; heat shock 70 kDa protein 6 [KO:K03283]
281534  TLR2; toll-like receptor 2 precursor [KO:K10159]
506387  LAMA1; laminin subunit alpha-1 isoform X1 [KO:K05637]
100138434  LAMA2; laminin subunit alpha-2 [KO:K05637]
506751  LAMA5; laminin subunit alpha-5 [KO:K06240]
100336873  LAMA3; laminin subunit alpha-3 isoform X4 [KO:K06240]
529670  LAMA4; laminin subunit alpha-4 precursor [KO:K06241]
520030  LAMB1; laminin subunit beta-1 precursor [KO:K05636]
530599  laminin subunit beta-2 isoform X1 [KO:K06243]
520167  LAMB2; laminin subunit beta-2 precursor [KO:K06243]
529939  LAMB3; laminin subunit beta-3 precursor [KO:K06244]
532572  LAMC1; laminin subunit gamma-1 precursor [KO:K05635]
511043  LAMC2; laminin subunit gamma-2 isoform X1 [KO:K06246]
518914  LAMC3; laminin subunit gamma-3 [KO:K06247]
535043  ITGA6; integrin alpha-6 precursor [KO:K06485]
281876  ITGB1; integrin beta-1 precursor [KO:K05719]
281276  LDLR; low-density lipoprotein receptor precursor [KO:K12473]
282527  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
507481  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
408016  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
510767  CYCS; cytochrome c [KO:K08738]
781996  CYCT; cytochrome c 2 [KO:K08738]
100847700  cytochrome c [KO:K08738]
100847304  cytochrome c-like [KO:K08738]
112447733  cytochrome c-like [KO:K08738]
100140945  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
281790  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
281791  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
539521  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
281792  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
530001  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
614838  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X3 [KO:K21290]
515621  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
100138102  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
534923  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
280991  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100137872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
615013  BAD; bcl2-associated agonist of cell death [KO:K02158]
282387  CD40LG; CD40 ligand [KO:K03161]
112445051  CD40 ligand [KO:K03161]
286849  CD40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
414346  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial precursor [KO:K09565] [EC:5.2.1.8]
497017  CCR5; C-C chemokine receptor type 5 [KO:K04180]
404074  ALOX5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
281246  IL10; interleukin-10 precursor [KO:K05443]
513478  IL10RA; interleukin-10 receptor subunit alpha precursor [KO:K05134]
767864  IL10RB; interleukin-10 receptor subunit beta precursor [KO:K05135]
512484  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
508541  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
282089  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
534069  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
538957  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
bta00590  Arachidonic acid metabolism
bta04010  MAPK signaling pathway
bta04144  Endocytosis
bta04210  Apoptosis
bta04620  Toll-like receptor signaling pathway
bta04630  JAK-STAT signaling pathway
KO pathway
ko05145   
LinkDB

DBGET integrated database retrieval system