KEGG   PATHWAY: rno05145
Entry
rno05145                    Pathway                                
Name
Toxoplasmosis - Rattus norvegicus (rat)
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
rno05145  Toxoplasmosis
rno05145

Disease
H00435  Toxoplasmosis
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100362733  Irgm2; interferon inducible GTPase 2 [KO:K14139] [EC:3.6.5.-]
108348108  Hspa1b; heat shock 70 kDa protein 1B [KO:K03283]
114495  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
114517  Itga6; integrin alpha-6 precursor [KO:K06485]
116465  Ifngr1; interferon gamma receptor 1 precursor [KO:K05132]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117029  Ccr5; C-C chemokine receptor type 5 [KO:K04180]
117036  Lamc1; laminin subunit gamma-1 precursor [KO:K05635]
117539  Il10ra; interleukin-10 receptor subunit alpha precursor [KO:K05134]
120099910  [KO:K08738]
140433  Lama5; laminin subunit alpha-5 precursor [KO:K06240]
171369  Cd40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
192362  Lamc2; laminin subunit gamma-2 precursor [KO:K06246]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
24468  Hspa8; heat shock cognate 71 kDa protein [KO:K03283]
24472  Hspa1a; heat shock 70 kDa protein 1A [KO:K03283]
24511  Itgb1; integrin beta-1 precursor [KO:K05719]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
24599  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
24835  Tnf; tumor necrosis factor [KO:K03156]
24888  Bcl2l1; bcl-2-like protein 1 isoform 2 [KO:K04570]
24963  Hspa1l; heat shock 70 kDa protein 1-like [KO:K03283]
24981  RT1-Db2; RT1 class II, locus Db2 precursor [KO:K06752]
24984  RT1-DOa; RT1 class II, locus DOa precursor [KO:K06752]
24986  RT1-Ha; RT1 class II, locus Ha precursor [KO:K06752]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
25125  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
25290  Alox5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
252971  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
25325  Il10; interleukin-10 precursor [KO:K05443]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
25473  Lamb2; laminin subunit beta-2 precursor [KO:K06243]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25712  Ifng; interferon gamma precursor [KO:K04687]
25717  Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377]
282819  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial precursor [KO:K09565] [EC:5.2.1.8]
290019  Cycsl3; cytochrome c, somatic-like [KO:K08738]
29260  Tlr4; toll-like receptor 4 precursor [KO:K10160]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
294269  RT1-Da; RT1 class II, locus Da precursor [KO:K06752]
294270  RT1-Db1; rano class II histocompatibility antigen, D-1 beta chain precursor [KO:K06752]
294273  RT1-DMb; RT1 class II, DM beta precursor [KO:K06752]
294274  RT1-DMa; RT1 class II, DM alpha precursor [KO:K06752]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
296468  Birc7; baculoviral IAP repeat-containing protein 7 [KO:K16061]
298941  Lamb1; laminin subunit beta-1 precursor [KO:K05636]
298947  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
300177  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
300438  Ldlr; low-density lipoprotein receptor precursor [KO:K12473]
301059  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
303090  Irgm; immunity-related GTPase family M protein [KO:K14139] [EC:3.6.5.-]
303163  Igtp; interferon gamma induced GTPase [KO:K14140]
303200  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
304091  Il10rb; interleukin-10 receptor subunit beta precursor [KO:K05135]
305078  Lamb3; laminin subunit beta-3 precursor [KO:K06244]
307582  Lama3; laminin subunit alpha-3 isoform B precursor [KO:K06240]
308267  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
309165  Rela; transcription factor p65 [KO:K04735]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
309368  Lama2; laminin subunit alpha-2 precursor [KO:K05637]
309621  RT1-Ba; rano class II histocompatibility antigen, B alpha chain precursor [KO:K06752]
309622  RT1-Bb; rano class II histocompatibility antigen, B-1 beta chain precursor [KO:K06752]
309816  Lama4; laminin subunit alpha-4 precursor [KO:K06241]
310553  Tlr2; toll-like receptor 2 precursor [KO:K10159]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
311862  Lamc3; laminin subunit gamma-3 precursor [KO:K06247]
313121  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
315139  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
316758  Lama1; laminin subunit alpha-1 precursor [KO:K05637]
360697  Ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
363520  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
365542  RT1-DOb; RT1 class II, DO beta isoform 1 [KO:K06752]
448830  Ly96; lymphocyte antigen 96 precursor [KO:K05400]
497931  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
497932  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
498491  Tlr11; toll-like receptor 11 [KO:K14142]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
60371  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
63879  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
679794  Cycsl1; cytochrome c, somatic-like [KO:K08738]
680121  Haus8l2; heat shock cognate 71 kDa protein-like [KO:K03283]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
690675  Cycsl2; cytochrome c, somatic-like [KO:K08738]
78971  Birc3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
84349  Cd40lg; CD40 ligand [KO:K03161]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
85483  Ciita; MHC class II transactivator isoform 2 [KO:K08060] [EC:2.7.11.1]
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
rno00590  Arachidonic acid metabolism
rno04010  MAPK signaling pathway
rno04144  Endocytosis
rno04210  Apoptosis
rno04620  Toll-like receptor signaling pathway
rno04630  JAK-STAT signaling pathway
KO pathway
ko05145   

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