KEGG   PATHWAY: mmu05145
Entry
mmu05145                    Pathway                                
Name
Toxoplasmosis - Mus musculus (house mouse)
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
mmu05145  Toxoplasmosis
mmu05145

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
15978  Ifng; interferon gamma [KO:K04687]
15979  Ifngr1; interferon gamma receptor 1 [KO:K05132]
15980  Ifngr2; interferon gamma receptor 2 [KO:K05133]
16451  Jak1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
16452  Jak2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
12265  Ciita; class II transactivator [KO:K08060] [EC:2.7.11.1]
14960  H2-Aa; histocompatibility 2, class II antigen A, alpha [KO:K06752]
14961  H2-Ab1; histocompatibility 2, class II antigen A, beta 1 [KO:K06752]
14969  H2-Eb1; histocompatibility 2, class II antigen E beta [KO:K06752]
14998  H2-DMa; histocompatibility 2, class II, locus DMa [KO:K06752]
14999  H2-DMb1; histocompatibility 2, class II, locus Mb1 [KO:K06752]
15000  H2-DMb2; histocompatibility 2, class II, locus Mb2 [KO:K06752]
15001  H2-Oa; histocompatibility 2, O region alpha locus [KO:K06752]
15002  H2-Ob; histocompatibility 2, O region beta locus [KO:K06752]
100504404  H2-Ea; histocompatibility 2, class II antigen E alpha [KO:K06752]
381091  H2-Eb2; histocompatibility 2, class II antigen E beta2 [KO:K06752]
15944  Irgm1; immunity-related GTPase family M member 1 [KO:K14139] [EC:3.6.5.-]
54396  Irgm2; immunity-related GTPase family M member 2 [KO:K14139] [EC:3.6.5.-]
16145  Igtp; interferon gamma induced GTPase [KO:K14140]
18126  Nos2; nitric oxide synthase 2, inducible [KO:K13241] [EC:1.14.13.39]
12703  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
239081  Tlr11; toll-like receptor 11 [KO:K14142]
17874  Myd88; myeloid differentiation primary response gene 88 [KO:K04729]
16179  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
266632  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
66513  Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
26397  Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
26399  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18036  Nfkbib; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta [KO:K02581]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
16159  Il12a; interleukin 12a [KO:K05406]
16160  Il12b; interleukin 12b [KO:K05425]
21926  Tnf; tumor necrosis factor [KO:K03156]
12043  Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
12048  Bcl2l1; BCL2-like 1 [KO:K04570]
11797  Birc2; baculoviral IAP repeat-containing 2 [KO:K16060]
11796  Birc3; baculoviral IAP repeat-containing 3 [KO:K16060]
11798  Xiap; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
329581  Birc7; baculoviral IAP repeat-containing 7 [KO:K16061]
17087  Ly96; lymphocyte antigen 96 [KO:K05400]
21898  Tlr4; toll-like receptor 4 [KO:K10160]
15481  Hspa8; heat shock protein 8 [KO:K03283]
15482  Hspa1l; heat shock protein 1-like [KO:K03283]
193740  Hspa1a; heat shock protein 1A [KO:K03283]
15511  Hspa1b; heat shock protein 1B [KO:K03283]
24088  Tlr2; toll-like receptor 2 [KO:K10159]
16772  Lama1; laminin, alpha 1 [KO:K05637]
16773  Lama2; laminin, alpha 2 [KO:K05637]
16774  Lama3; laminin, alpha 3 [KO:K06240]
16776  Lama5; laminin, alpha 5 [KO:K06240]
16775  Lama4; laminin, alpha 4 [KO:K06241]
16777  Lamb1; laminin B1 [KO:K05636]
16779  Lamb2; laminin, beta 2 [KO:K06243]
16780  Lamb3; laminin, beta 3 [KO:K06244]
226519  Lamc1; laminin, gamma 1 [KO:K05635]
16782  Lamc2; laminin, gamma 2 [KO:K06246]
23928  Lamc3; laminin gamma 3 [KO:K06247]
16403  Itga6; integrin alpha 6 [KO:K06485]
16412  Itgb1; integrin beta 1 (fibronectin receptor beta) [KO:K05719]
16835  Ldlr; low density lipoprotein receptor [KO:K12473]
21937  Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
12370  Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
12367  Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
13063  Cycs; cytochrome c, somatic [KO:K08738]
13067  Cyct; cytochrome c, testis [KO:K08738]
12371  Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
14677  Gnai1; G protein subunit alpha i1 [KO:K04630]
14679  Gnai3; G protein subunit alpha i3 [KO:K04630]
14678  Gnai2; G protein subunit alpha i2 [KO:K04630]
14681  Gnao1; guanine nucleotide binding protein, alpha O [KO:K04534]
30955  Pik3cg; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
320207  Pik3r5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
104709  Pik3r6; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
18607  Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
12015  Bad; BCL2-associated agonist of cell death [KO:K02158]
21947  Cd40lg; CD40 ligand [KO:K03161]
21939  Cd40; CD40 antigen [KO:K03160]
105675  Ppif; peptidylprolyl isomerase F (cyclophilin F) [KO:K09565] [EC:5.2.1.8]
12774  Ccr5; C-C motif chemokine receptor 5 [KO:K04180]
11689  Alox5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
16153  Il10; interleukin 10 [KO:K05443]
16154  Il10ra; interleukin 10 receptor, alpha [KO:K05134]
16155  Il10rb; interleukin 10 receptor, beta [KO:K05135]
54721  Tyk2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
20848  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  Tgfb3; transforming growth factor, beta 3 [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
mmu00590  Arachidonic acid metabolism
mmu04010  MAPK signaling pathway
mmu04144  Endocytosis
mmu04210  Apoptosis
mmu04620  Toll-like receptor signaling pathway
mmu04630  JAK-STAT signaling pathway
KO pathway
ko05145   
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