KEGG   PATHWAY: mun05145
mun05145                    Pathway                                

Toxoplasmosis - Meriones unguiculatus (Mongolian gerbil)
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.
Human Diseases; Infectious disease: parasitic
Pathway map
mun05145  Toxoplasmosis

Meriones unguiculatus (Mongolian gerbil) [GN:mun]
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:]
110547004  Jak2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:]
110552020  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
110555272  Ciita; MHC class II transactivator isoform X1 [KO:K08060] [EC:]
110543060  class II histocompatibility antigen, M alpha chain [KO:K06752]
110543088  class II histocompatibility antigen, M beta 1 chain [KO:K06752]
110543117  LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, E-D beta chain-like [KO:K06752]
110543181  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
110543223  LOW QUALITY PROTEIN: 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 X1 [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 X1 [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-like isoform X1 [KO:K14139] [EC:3.6.5.-]
110550157  Nos2; nitric oxide synthase, inducible isoform X1 [KO:K13241] [EC:]
110555271  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
110555059  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
110566945  Irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:]
110563636  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:]
110557497  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:]
110565808  mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
110565809  mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:]
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 [KO:K04371] [EC:]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
110561677  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:]
110563014  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:]
110563015  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:]
110546562  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
110546585  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
110549680  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:]
110549673  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:]
110562528  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
110562401  Nfkbia; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
110552558  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110549347  Rela; transcription factor p65 [KO:K04735]
110557307  Il12a; interleukin-12 subunit alpha [KO:K05406]
110548438  Il12b; interleukin-12 subunit beta [KO:K05425]
110560136  Tnf; 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  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
110542115  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:]
110554792  baculoviral IAP repeat-containing protein 7-like [KO:K16061]
110554754  baculoviral IAP repeat-containing protein 7-like [KO:K16061]
110565332  Tlr4; toll-like receptor 4 [KO:K10160]
110560143  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
110560130  Hspa1a; heat shock 70 kDa protein 1A isoform X1 [KO:K03283]
110547779  Hspa2; heat shock-related 70 kDa protein 2 [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]
110559223  Lama2; laminin subunit alpha-2 [KO:K05637]
110552295  Lama1; laminin subunit alpha-1 [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 isoform X1 [KO:K05636]
110565216  Lamb2; laminin subunit beta-2 [KO:K06243]
110559812  Lamb3; laminin subunit beta-3 [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]
110563279  integrin alpha-6 [KO:K06485]
110563280  integrin alpha-6 isoform X1 [KO:K06485]
110554841  Itgb1; integrin beta-1 [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 [KO:K04398] [EC:]
110545164  cytochrome c, somatic [KO:K08738]
110555979  cytochrome c, testis-specific [KO:K08738]
110545060  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:]
110539607  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
110545517  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
110564775  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
110565083  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:]
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:]
110556719  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
110564898  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
110551603  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110561796  Cd40lg; CD40 ligand isoform X1 [KO:K03161]
110549441  Cd40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
110565488  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:]
110566894  C-C chemokine receptor type 5 [KO:K04180]
110563686  arachidonate 5-lipoxygenase [KO:K00461] [EC:]
110563694  arachidonate 5-lipoxygenase [KO:K00461] [EC:]
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:]
110550916  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
110561197  Tgfb1; transforming growth factor beta-1 [KO:K13375]
110549244  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
110558214  Tgfb3; transforming growth factor beta-3 [KO:K13377]
C00076  Calcium cation
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06314  Lipoxin A4
Denkers EY, Butcher BA
Sabotage and exploitation in macrophages parasitized by intracellular protozoans.
Trends Parasitol 21:35-41 (2005)
Denkers EY
From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii.
FEMS Immunol Med Microbiol 39:193-203 (2003)
Pollard AM, Knoll LJ, Mordue DG
The role of specific Toxoplasma gondii molecules in manipulation of innate immunity.
Trends Parasitol 25:491-4 (2009)
Leng J, Butcher BA, Denkers EY
Dysregulation of macrophage signal transduction by Toxoplasma gondii: past progress and recent advances.
Parasite Immunol 31:717-28 (2009)
Miller CM, Boulter NR, Ikin RJ, Smith NC
The immunobiology of the innate response to Toxoplasma gondii.
Int J Parasitol 39:23-39 (2009)
Denkers EY, Kim L, Butcher BA
In the belly of the beast: subversion of macrophage proinflammatory signalling cascades during Toxoplasma gondii infection.
Cell Microbiol 5:75-83 (2003)
Gazzinelli RT, Denkers EY
Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.
Nat Rev Immunol 6:895-906 (2006)
Lang C, Gross U, Luder CG
Subversion of innate and adaptive immune responses by Toxoplasma gondii.
Parasitol Res 100:191-203 (2007)
Blader IJ, Saeij JP
Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence.
APMIS 117:458-76 (2009)
Boothroyd JC, Dubremetz JF
Kiss and spit: the dual roles of Toxoplasma rhoptries.
Nat Rev Microbiol 6:79-88 (2008)
Denkers EY, Butcher BA, Del Rio L, Kim L
Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signaling cascades during intracellular Toxoplasma gondii infection.
Immunol Rev 201:191-205 (2004)
Yarovinsky F
Toll-like receptors and their role in host resistance to Toxoplasma gondii.
Immunol Lett 119:17-21 (2008)
Coppens I, Joiner KA
Parasitehost cell interactions in toxoplasmosis: new avenues for intervention?
Expert Rev Mol Med 2001:1-20 (2001)
Aliberti J, Sher A
Role of G-protein-coupled signaling in the induction and regulation of dendritic cell function by Toxoplasma gondii.
Microbes Infect 4:991-7 (2002)
Sher A, Collazzo C, Scanga C, Jankovic D, Yap G, Aliberti J
Induction and regulation of IL-12-dependent host resistance to Toxoplasma gondii.
Immunol Res 27:521-8 (2003)
Bonhomme A, Bouchot A, Pezzella N, Gomez J, Le Moal H, Pinon JM
Signaling during the invasion of host cells by Toxoplasma gondii.
FEMS Microbiol Rev 23:551-61 (1999)
Laliberte J, Carruthers VB
Host cell manipulation by the human pathogen Toxoplasma gondii.
Cell Mol Life Sci 65:1900-15 (2008)
Bogdan C, Rollinghoff M
How do protozoan parasites survive inside macrophages?
Parasitol Today 15:22-8 (1999)
Molestina RE, Sinai AP
Host and parasite-derived IKK activities direct distinct temporal phases of NF-kappaB activation and target gene expression following Toxoplasma gondii infection.
J Cell Sci 118:5785-96 (2005)
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

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