KEGG   PATHWAY: dro05145
Entry
dro05145                    Pathway                                
Name
Toxoplasmosis - Desmodus rotundus (common vampire 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
dro05145  Toxoplasmosis
dro05145

Organism
Desmodus rotundus (common vampire bat) [GN:dro]
Gene
112319176  IFNG; interferon gamma [KO:K04687]
112297082  IFNGR1; interferon gamma receptor 1 [KO:K05132]
112308734  IFNGR2; interferon gamma receptor 2 [KO:K05133]
112309187  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
112299737  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
112307780  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
112314942  CIITA; MHC class II transactivator [KO:K08060] [EC:2.7.11.1]
112302159  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
112302160  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
112302240  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
112302328  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
112302354  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
112308600  NOS2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
112314971  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
112311095  LOW QUALITY PROTEIN: toll-like receptor 11 [KO:K14142]
112309628  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
112296346  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
112318391  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
112303407  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
112296959  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
112322023  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
112297111  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112308621  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
112316519  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
112302047  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
112321896  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
112302140  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
112322057  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
112300474  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
112321547  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
112296261  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112296519  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112320245  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
112317867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112317202  RELA; transcription factor p65 [KO:K04735]
112304655  IL12A; interleukin-12 subunit alpha [KO:K05406]
112319648  IL12B; interleukin-12 subunit beta [KO:K05425]
112302067  TNF; tumor necrosis factor isoform X1 [KO:K03156]
112322759  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
112304196  BCL2L1; bcl-2-like protein 1 [KO:K04570]
112317544  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
112317519  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
112310530  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
112303893  BIRC7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
112320863  LY96; lymphocyte antigen 96 [KO:K05400]
112306266  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
112301823  HSPA8; LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein [KO:K03283]
112302142  heat shock 70 kDa protein 1 [KO:K03283]
112302152  heat shock 70 kDa protein 1-like [KO:K03283]
112312607  TLR2; toll-like receptor 2 [KO:K10159]
112322610  LAMA1; laminin subunit alpha-1 [KO:K05637]
112297058  LAMA2; laminin subunit alpha-2 [KO:K05637]
112322675  laminin subunit alpha-3-like [KO:K06240]
112303887  LAMA5; laminin subunit alpha-5 [KO:K06240]
112302957  LAMB1; laminin subunit beta-1 [KO:K05636]
112309635  LAMB2; laminin subunit beta-2 [KO:K06243]
112309774  LOW QUALITY PROTEIN: laminin subunit beta-2-like [KO:K06243]
112297463  LAMB3; laminin subunit beta-3 [KO:K06244]
112302299  LAMB4; laminin subunit beta-4 [KO:K06245]
112297926  LAMC1; laminin subunit gamma-1 [KO:K05635]
112296770  LAMC2; laminin subunit gamma-2 [KO:K06246]
112306548  LAMC3; laminin subunit gamma-3 [KO:K06247]
112305805  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
112317701  ITGB1; integrin beta-1 [KO:K05719]
112301407  LDLR; low-density lipoprotein receptor [KO:K12473]
112321955  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
112307787  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
112306749  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
112306993  cytochrome c [KO:K08738]
112320658  cytochrome c-like [KO:K08738]
112322221  cytochrome c-like [KO:K08738]
112299456  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
112313520  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
112303430  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
112309828  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
112296672  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
112303039  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
112308895  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
112308643  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
112298319  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112317275  BAD; bcl2-associated agonist of cell death [KO:K02158]
112307303  CD40LG; CD40 ligand isoform X1 [KO:K03161]
112304112  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
112305493  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
112309611  C-C chemokine receptor type 5-like [KO:K04180]
112305481  ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
112315005  IL10; interleukin-10 [KO:K05443]
112314321  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
112305545  IL10RB; interleukin-10 receptor subunit beta [KO:K05135]
112301524  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
112298562  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
112320009  TGFB1; transforming growth factor beta-1 [KO:K13375]
112318906  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
112311221  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
dro00590  Arachidonic acid metabolism
dro04010  MAPK signaling pathway
dro04144  Endocytosis
dro04210  Apoptosis
dro04620  Toll-like receptor signaling pathway
dro04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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