KEGG   PATHWAY: lav05145
Entry
lav05145                    Pathway                                
Name
Toxoplasmosis - Loxodonta africana (African savanna elephant)
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
lav05145  Toxoplasmosis
lav05145

Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100663285  IFNG; interferon gamma [KO:K04687]
100665172  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100667304  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
100655548  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100676652  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
100668424  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100664680  CIITA; MHC class II transactivator isoform X8 [KO:K08060] [EC:2.7.11.1]
100672091  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
100672379  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
100664409  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
100665293  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
100662176  HLA class II histocompatibility antigen, DP alpha 1 chain-like isoform X4 [KO:K06752]
100668794  HLA class II histocompatibility antigen, DQ beta 2 chain-like isoform X2 [KO:K06752]
100673529  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
100675728  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
100669075  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
100666146  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
100665860  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
100675445  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
100667002  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
100664981  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
100665266  LOW QUALITY PROTEIN: mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
100671834  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
111748122  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
100672669  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
100674958  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
100665550  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
100665834  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111748125  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
100671798  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
100673824  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
100659676  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
100667174  IRGM; immunity-related GTPase family M protein isoform X2 [KO:K14139] [EC:3.6.5.-]
100669062  LOW QUALITY PROTEIN: immunity-related GTPase family M protein-like [KO:K14139] [EC:3.6.5.-]
100676634  NOS2; LOW QUALITY PROTEIN: nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
100664110  SOCS1; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1 [KO:K04694]
100655137  toll-like receptor 11 [KO:K14142]
100659447  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
100676181  IRAK1; LOW QUALITY PROTEIN: interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
100653528  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
100671471  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100667170  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X2 [KO:K04427] [EC:2.7.11.25]
100660911  TAB1; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
100656450  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X2 [KO:K04404]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100654943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100674229  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100673395  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100675607  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
100662511  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
100673331  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100656926  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100661039  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100664361  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100657363  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3 [KO:K07209] [EC:2.7.11.10]
100661492  IKBKG; LOW QUALITY PROTEIN: NF-kappa-B essential modulator [KO:K07210]
100675651  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100657581  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
100662194  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100654730  RELA; transcription factor p65 isoform X2 [KO:K04735]
100665137  IL12A; interleukin-12 subunit alpha [KO:K05406]
100657211  IL12B; interleukin-12 subunit beta [KO:K05425]
100677125  TNF; tumor necrosis factor isoform X2 [KO:K03156]
100675268  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100655646  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100659163  baculoviral IAP repeat-containing protein 3 [KO:K16060]
100659446  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
100657657  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100654401  LY96; lymphocyte antigen 96 isoform X1 [KO:K05400]
100654493  TLR4; toll-like receptor 4 [KO:K10160]
100669335  HSPA1A; heat shock 70 kDa protein 1A [KO:K03283]
100669618  heat shock 70 kDa protein 1-like [KO:K03283]
100663257  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
104847136  heat shock 70 kDa protein 1-like [KO:K03283]
100656420  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
100654442  TLR2; toll-like receptor 2 [KO:K10159]
100672596  LAMA1; laminin subunit alpha-1 [KO:K05637]
100677404  LAMA2; laminin subunit alpha-2 [KO:K05637]
104845537  LAMA3; laminin subunit alpha-3 [KO:K06240]
100676944  LAMA5; LOW QUALITY PROTEIN: laminin subunit alpha-5 [KO:K06240]
111749628  laminin subunit alpha-3-like [KO:K06240]
100662531  LAMA4; LOW QUALITY PROTEIN: laminin subunit alpha-4 [KO:K06241]
100675837  LAMB1; laminin subunit beta-1 isoform X1 [KO:K05636]
100655070  LAMB2; laminin subunit beta-2 [KO:K06243]
100666736  LAMB3; LOW QUALITY PROTEIN: laminin subunit beta-3 [KO:K06244]
100658659  LAMB4; LOW QUALITY PROTEIN: laminin subunit beta-4 [KO:K06245]
100671561  LAMC1; laminin subunit gamma-1 [KO:K05635]
100661346  LAMC2; laminin subunit gamma-2 [KO:K06246]
100670126  LAMC3; LOW QUALITY PROTEIN: laminin subunit gamma-3 [KO:K06247]
100661035  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100664978  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100669109  LDLR; low-density lipoprotein receptor isoform X2 [KO:K12473]
100672143  TNFRSF1A; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100663575  caspase-8 [KO:K04398] [EC:3.4.22.61]
100660542  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
100672256  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
100654286  cytochrome c, testis-specific [KO:K08738]
100657132  cytochrome c [KO:K08738]
100656597  CASP9; caspase-9 isoform X3 [KO:K04399] [EC:3.4.22.62]
100666344  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100670234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100667957  GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100658419  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
100673566  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
100670067  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
100674744  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
100660030  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100663184  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100657536  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100660187  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100668387  BAD; bcl2-associated agonist of cell death [KO:K02158]
100659000  CD40LG; CD40 ligand [KO:K03161]
100666178  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
100668630  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
100169649  CCR5; chemokine (C-C motif) receptor 5 [KO:K04180]
100661336  ALOX5; arachidonate 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
100665398  IL10; interleukin-10 isoform X2 [KO:K05443]
100677387  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
100667872  IL10RB; interleukin-10 receptor subunit beta isoform X2 [KO:K05135]
100672245  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100669583  STAT3; signal transducer and activator of transcription 3 isoform X2 [KO:K04692]
100667634  TGFB1; transforming growth factor beta-1 [KO:K13375]
100656534  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
100653832  TGFB3; transforming growth factor beta-3 isoform X1 [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
lav00590  Arachidonic acid metabolism
lav04010  MAPK signaling pathway
lav04144  Endocytosis
lav04210  Apoptosis
lav04620  Toll-like receptor signaling pathway
lav04630  JAK-STAT signaling pathway
KO pathway
ko05145   
LinkDB

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