KEGG   PATHWAY: ko05145Help
Entry
ko05145                     Pathway                                

Name
Toxoplasmosis
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 diseases: Parasitic
BRITE hierarchy
Pathway map
ko05145  Toxoplasmosis
ko05145

Ortholog table
Disease
H00435  Toxoplasmosis
Orthology
K04687  interferon gamma
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K11217  Janus kinase 1 [EC:2.7.10.2]
K04447  Janus kinase 2 [EC:2.7.10.2]
K11220  signal transducer and activator of transcription 1
K08060  class II, major histocompatibility complex, transactivator
K06752  major histocompatibility complex, class II
K14139  immunity-related GTPase family M protein [EC:3.6.5.-]
K14140  interferon gamma induced GTPase
K13241  nitric-oxide synthase, inducible [EC:1.14.13.39]
K04694  suppressor of cytokine signaling 1
K14141  profilin-like protein
K14142  toll-like receptor 11
K04729  myeloid differentiation primary response protein MyD88
K04730  interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04733  interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K03175  TNF receptor-associated factor 6 [EC:2.3.2.27]
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04403  TAK1-binding protein 1
K04404  TAK1-binding protein 2
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04432  mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04441  p38 MAP kinase [EC:2.7.11.24]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734  NF-kappa-B inhibitor alpha
K02581  NF-kappa-B inhibitor beta
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K05406  interleukin 12A
K05425  interleukin 12B
K03156  tumor necrosis factor superfamily, member 2
K02161  apoptosis regulator Bcl-2
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K16060  baculoviral IAP repeat-containing protein 2/3
K04725  E3 ubiquitin-protein ligase XIAP [EC:2.3.2.27]
K16061  baculoviral IAP repeat-containing protein 7/8
K05400  lymphocyte antigen 96
K10160  toll-like receptor 4
K03283  heat shock 70kDa protein 1/2/6/8
K10159  toll-like receptor 2
K05637  laminin, alpha 1/2
K06240  laminin, alpha 3/5
K06241  laminin, alpha 4
K05636  laminin, beta 1
K06243  laminin, beta 2
K06244  laminin, beta 3
K06245  laminin, beta 4
K05635  laminin, gamma 1
K06246  laminin, gamma 2
K06247  laminin, gamma 3
K06485  integrin alpha 6
K05719  integrin beta 1
K14143  major surface antigen
K14144  microneme protein
K13412  calcium-dependent protein kinase [EC:2.7.11.1]
K13845  apical merozoite antigen 1
K14145  rhoptry neck protein 2
K14146  rhoptry neck protein 4
K12473  low-density lipoprotein receptor
K14147  dense granule protein 7
K14148  rhoptry protein 2
K14149  dense granule protein 3
K14150  dense granule protein 5
K03158  tumor necrosis factor receptor superfamily member 1A
K04398  caspase 8 [EC:3.4.22.61]
K02187  caspase 3 [EC:3.4.22.56]
K08738  cytochrome c
K04399  caspase 9 [EC:3.4.22.62]
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K04534  guanine nucleotide-binding protein G(o) subunit alpha
K21289  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153]
K21290  phosphoinositide-3-kinase regulatory subunit 5/6
K06276  3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K02158  Bcl-2-antagonist of cell death
K03161  tumor necrosis factor ligand superfamily member 5
K03160  tumor necrosis factor receptor superfamily member 5
K09565  peptidyl-prolyl isomerase F (cyclophilin D) [EC:5.2.1.8]
K04180  C-C chemokine receptor type 5
K00461  arachidonate 5-lipoxygenase [EC:1.13.11.34]
K14151  rhoptry protein 16
K05443  interleukin 10
K05134  interleukin 10 receptor alpha
K05135  interleukin 10 receptor beta
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]
K04692  signal transducer and activator of transcription 3
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
Compound
C00076  Calcium cation
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06314  Lipoxin A4
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
LinkDB All DBs

DBGET integrated database retrieval system