KEGG   PATHWAY: mun05145
Entry
mun05145                    Pathway                                
Name
Toxoplasmosis - Meriones unguiculatus (Mongolian gerbil)
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
mun05145  Toxoplasmosis
mun05145

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110561827  Ifng; interferon gamma [KO:K04687]
110557641  Ifngr1; interferon gamma receptor 1 [KO:K05132]
110541673  Ifngr2; interferon gamma receptor 2 [KO:K05133]
110555551  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
110547004  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
110552020  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
110555272  Ciita; MHC class II transactivator isoform X3 [KO:K08060] [EC:2.7.11.1]
110543060  class II histocompatibility antigen, M alpha chain [KO:K06752]
110543088  class II histocompatibility antigen, M beta 1 chain isoform X1 [KO:K06752]
110543117  H-2 class II histocompatibility antigen, E-D beta chain-like isoform X1 [KO:K06752]
110543181  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
110543223  H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
110543234  rano class II histocompatibility antigen, B-1 beta chain-like [KO:K06752]
110543301  HLA class II histocompatibility antigen, DP beta 1 chain-like isoform X2 [KO:K06752]
110543331  RLA class II histocompatibility antigen, DP alpha-1 chain isoform X1 [KO:K06752]
110544088  H-2 class II histocompatibility antigen, A-F alpha chain [KO:K06752]
110542965  HLA class II histocompatibility antigen, DO beta chain isoform X2 [KO:K06752]
110543034  H-2 class II histocompatibility antigen, E-U alpha chain-like [KO:K06752]
110551033  immunity-related GTPase family M protein 1-like isoform X1 [KO:K14139] [EC:3.6.5.-]
110563362  immunity-related GTPase family M protein 2-like isoform X1 [KO:K14139] [EC:3.6.5.-]
110550157  Nos2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:1.14.13.39]
110555271  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
110555059  Myd88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
110566945  Irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
110563636  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
110557497  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110565808  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110557813  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
110540621  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110562875  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110561677  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
110563015  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
110546562  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110546585  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110549680  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110549673  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110544653  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110552558  Nfkbib; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110557307  Il12a; interleukin-12 subunit alpha [KO:K05406]
110548438  Il12b; interleukin-12 subunit beta [KO:K05425]
110560136  Tnf; LOW QUALITY PROTEIN: tumor necrosis factor [KO:K03156]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110550083  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
110553751  Birc3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
110553757  Birc2; baculoviral IAP repeat-containing protein 2 isoform X4 [KO:K16060]
110542115  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110554792  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
132654750  Ly96; lymphocyte antigen 96 [KO:K05400]
110565332  Tlr4; toll-like receptor 4 [KO:K10160]
110560143  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
110560130  heat shock 70 kDa protein 1A [KO:K03283]
110552032  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
110554439  Hspa6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
110541773  Tlr2; toll-like receptor 2 [KO:K10159]
110552295  Lama1; laminin subunit alpha-1 [KO:K05637]
110559223  Lama2; laminin subunit alpha-2 [KO:K05637]
110554009  Lama5; laminin subunit alpha-5 [KO:K06240]
110553478  Lama3; laminin subunit alpha-3 isoform X1 [KO:K06240]
110564967  Lama4; laminin subunit alpha-4 [KO:K06241]
110558987  Lamb1; laminin subunit beta-1 [KO:K05636]
110565216  Lamb2; laminin subunit beta-2 [KO:K06243]
110559812  Lamb3; laminin subunit beta-3 isoform X3 [KO:K06244]
110546189  Lamc1; laminin subunit gamma-1 [KO:K05635]
110546194  Lamc2; laminin subunit gamma-2 [KO:K06246]
110559252  Lamc3; laminin subunit gamma-3 isoform X1 [KO:K06247]
110563280  Itga6; integrin alpha-6 isoform X3 [KO:K06485]
110554841  Itgb1; integrin beta-1 isoform X2 [KO:K05719]
110552462  Ldlr; low-density lipoprotein receptor isoform X1 [KO:K12473]
110548604  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
110557662  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
132653623  Casp3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
110545164  cytochrome c, somatic [KO:K08738]
110555979  cytochrome c, testis-specific [KO:K08738]
110563439  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
110559601  cytochrome c, somatic-like [KO:K08738]
110549868  LOW QUALITY PROTEIN: cytochrome c, somatic-like [KO:K08738]
110552819  cytochrome c, somatic-like [KO:K08738]
110545060  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
110539607  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
110545517  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
110564775  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
110561150  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110565083  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
110551705  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
110551706  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
110553013  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110551603  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110561796  Cd40lg; CD40 ligand [KO:K03161]
110549441  Cd40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
110565488  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial isoform X2 [KO:K09565] [EC:5.2.1.8]
110566894  C-C chemokine receptor type 5 [KO:K04180]
110563694  Alox5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
110550319  Il10; interleukin-10 [KO:K05443]
110549113  Il10ra; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
110541906  Il10rb; interleukin-10 receptor subunit beta [KO:K05135]
110555765  Tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
110550916  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
110561197  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
110549244  Tgfb2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
110558214  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
mun00590  Arachidonic acid metabolism
mun04010  MAPK signaling pathway
mun04144  Endocytosis
mun04210  Apoptosis
mun04620  Toll-like receptor signaling pathway
mun04630  JAK-STAT signaling pathway
KO pathway
ko05145   
LinkDB

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