KEGG   PATHWAY: ocu05145
Entry
ocu05145                    Pathway                                
Name
Toxoplasmosis - Oryctolagus cuniculus (rabbit)
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
ocu05145  Toxoplasmosis
ocu05145

Disease
H00435  Toxoplasmosis
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008602  IFNG; interferon gamma precursor [KO:K04687]
100008642  [KO:K06485]
100008645  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
100008701  IL10; interleukin-10 precursor [KO:K05443]
100008833  [KO:K13241] [EC:1.14.13.39]
100008840  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100008875  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100008898  [KO:K05719]
100009086  LDLR; low-density lipoprotein receptor precursor [KO:K12473]
100009088  TNF; tumor necrosis factor precursor [KO:K03156]
100009371  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
100009388  [KO:K06243]
100009497  TLR4; toll-like receptor 4 [KO:K10160]
100009578  TLR2; toll-like receptor 2 precursor [KO:K10159]
100009589  LY96; lymphocyte antigen 96 precursor [KO:K05400]
100101579  CCR5; C-C chemokine receptor type 5 [KO:K04180]
100101592  [KO:K04399] [EC:3.4.22.62]
100328700  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100328905  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100328929  RLA-DR-ALPHA; major histocompatibility complex, class II, DR alpha precursor [KO:K06752]
100337757  [KO:K21290]
100337999  [KO:K04440] [EC:2.7.11.24]
100338118  [KO:K16060]
100338160  [KO:K03283]
100338351  [KO:K05135]
100338362  [KO:K09565] [EC:5.2.1.8]
100338391  [KO:K04630]
100338854  [KO:K05133]
100338894  [KO:K08060] [EC:2.7.11.1]
100339066  [KO:K04630]
100339386  [KO:K04694]
100339627  [KO:K16061]
100339953  [KO:K04432] [EC:2.7.12.2]
100340120  [KO:K16060]
100340526  [KO:K21290]
100340811  [KO:K04729]
100341050  [KO:K08738]
100341175  [KO:K08738]
100341358  [KO:K06752]
100341515  [KO:K08738]
100341605  [KO:K04733] [EC:2.7.11.1]
100341695  [KO:K04441] [EC:2.7.11.24]
100341714  [KO:K00461] [EC:1.13.11.34]
100341787  [KO:K05132]
100342249  [KO:K04404]
100342275  [KO:K14139] [EC:3.6.5.-]
100342283  [KO:K04534]
100342664  [KO:K04440] [EC:2.7.11.24]
100342852  [KO:K04456] [EC:2.7.11.1]
100342905  LAMB3; laminin subunit beta-3 precursor [KO:K06244]
100343144  [KO:K06752]
100343190  [KO:K03175] [EC:2.3.2.27]
100343571  [KO:K04427] [EC:2.7.11.25]
100343893  [KO:K11220]
100344144  [KO:K21289] [EC:2.7.1.153]
100344161  [KO:K04441] [EC:2.7.11.24]
100344622  [KO:K11219] [EC:2.7.10.2]
100345253  [KO:K04725] [EC:2.3.2.27]
100346106  [KO:K03158]
100346886  [KO:K06240]
100346929  [KO:K04440] [EC:2.7.11.24]
100347345  [KO:K04371] [EC:2.7.11.24]
100347922  [KO:K14142]
100347954  [KO:K06276] [EC:2.7.11.1]
100348477  [KO:K04398] [EC:3.4.22.61]
100348561  [KO:K04371] [EC:2.7.11.24]
100348778  [KO:K04692]
100348873  [KO:K03283]
100349007  [KO:K05406]
100349106  [KO:K03160]
100349408  [KO:K06752]
100349426  [KO:K02580]
100349667  [KO:K06752]
100350168  [KO:K06752]
100350500  [KO:K05637]
100350614  [KO:K04441] [EC:2.7.11.24]
100350656  RLA-DRB1; HLA class II histocompatibility antigen, DRB1 beta chain [KO:K06752]
100351037  [KO:K08738]
100351163  [KO:K06752]
100351387  [KO:K05635]
100351416  [KO:K06752]
100352301  [KO:K13375]
100352415  RLA-DMA; histocompatibility antigen DM heterodimer heavy chain-like precursor [KO:K06752]
100352594  [KO:K11217] [EC:2.7.10.2]
100352672  [KO:K06752]
100352927  [KO:K06752]
100353534  [KO:K03283]
100353673  [KO:K08738]
100353706  [KO:K04456] [EC:2.7.11.1]
100354037  [KO:K03283]
100354435  [KO:K03283]
100354468  [KO:K08738]
100354724  [KO:K08738]
100354743  [KO:K04730] [EC:2.7.11.1]
100354852  [KO:K05425]
100354902  [KO:K05134]
100355084  [KO:K08738]
100355230  [KO:K04433] [EC:2.7.12.2]
100355888  [KO:K04467] [EC:2.7.11.10]
100355948  RLA-DMB; histocompatibility antigen DM heterodimer light chain-like precursor [KO:K06752]
100356401  [KO:K07209] [EC:2.7.11.10]
100356572  [KO:K03283]
100357329  [KO:K08738]
100357341  [KO:K04734]
100357482  [KO:K05637]
100357840  [KO:K08738]
100358134  [KO:K04447] [EC:2.7.10.2]
100358246  [KO:K04403]
100358388  CD40LG; CD40 ligand [KO:K03161]
100358587  [KO:K02158]
100358679  [KO:K05636]
100358982  [KO:K13377]
100359147  [KO:K04630]
100359283  [KO:K02581]
103345292  [KO:K06247]
103345448  [KO:K13375]
103346035  [KO:K04441] [EC:2.7.11.24]
103347398  [KO:K06240]
103347723  [KO:K08738]
103349397  [KO:K02161]
108175836  [KO:K08738]
108177422  [KO:K08738]
108177458  [KO:K06241]
108178730  [KO:K08738]
127482571  [KO:K06752]
127483320  [KO:K08738]
127485184  [KO:K04735]
127486116  [KO:K04456] [EC:2.7.11.1]
127488889  [KO:K03283]
127488890  [KO:K03283]
127488928  [KO:K11220]
127493068  [KO:K03283]
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
ocu00590  Arachidonic acid metabolism
ocu04010  MAPK signaling pathway
ocu04144  Endocytosis
ocu04210  Apoptosis
ocu04620  Toll-like receptor signaling pathway
ocu04630  JAK-STAT signaling pathway
KO pathway
ko05145   

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