Entry Name Toxoplasmosis
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: parasiticBRITE hierarchy
Pathway map Disease Orthology K02158 BAD; Bcl-2-antagonist of cell death
K02161 BCL2; apoptosis regulator Bcl-2
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581 NFKBIB; NF-kappa-B inhibitor beta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03160 TNFRSF5, CD40; tumor necrosis factor receptor superfamily member 5
K03161 TNFSF5, CD40L, CD154; tumor necrosis factor ligand superfamily member 5
K03283 HSPA1_6_8; heat shock 70kDa protein 1/6/8
K04180 CCR5, CD195; C-C chemokine receptor type 5
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04534 GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha
K04570 BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04630 GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04692 STAT3; signal transducer and activator of transcription 3
K04694 SOCS1, JAB; suppressor of cytokine signaling 1
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K05132 IFNGR1, CD119; interferon gamma receptor 1
K05133 IFNGR2; interferon gamma receptor 2
K05134 IL10RA, CD210A; interleukin 10 receptor alpha
K05135 IL10RB, CD210B; interleukin 10 receptor beta
K05400 LY96, MD-2; lymphocyte antigen 96
K05443 IL10, CSIF; interleukin 10
K05635 LAMC1; laminin, gamma 1
K05637 LAMA1_2; laminin, alpha 1/2
K05719 ITGB1, CD29; integrin beta 1
K06240 LAMA3_5; laminin, alpha 3/5
K06241 LAMA4; laminin, alpha 4
K06246 LAMC2; laminin, gamma 2
K06247 LAMC3; laminin, gamma 3
K06276 PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1 ]
K06485 ITGA6, CD49f; integrin alpha 6
K06752 MHC2; MHC class II antigen
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K09565 PPIF; peptidyl-prolyl isomerase F (cyclophilin D) [EC:5.2.1.8 ]
K10159 TLR2, CD282; toll-like receptor 2
K10160 TLR4, CD284; toll-like receptor 4
K11220 STAT1; signal transducer and activator of transcription 1
K12473 LDLR; low-density lipoprotein receptor
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K13377 TGFB3; transforming growth factor beta-3
K13845 AMA-1; apical merozoite antigen 1
K14139 IRGM, LRG47; immunity-related GTPase family M protein [EC:3.6.5.-]
K14140 IGTP; interferon gamma induced GTPase
K14141 PFNL; profilin-like protein
K14142 TLR11; toll-like receptor 11
K14143 SAG; major surface antigen
K14144 MIC3; microneme protein
K14145 RON2; rhoptry neck protein 2
K14146 RON4; rhoptry neck protein 4
K14147 GRA7; dense granule protein 7
K14148 ROP2; rhoptry protein 2
K14149 GRA3; dense granule protein 3
K14150 GRA5; dense granule protein 5
K14151 ROP16; rhoptry protein 16
K16060 BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16061 BIRC7_8; baculoviral IAP repeat-containing protein 7/8
K21289 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153 ]
K21290 PIK3R5_6; phosphoinositide-3-kinase regulatory subunit 5/6
K23534 PP2CHN; protein phosphatase
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Denkers EY, Butcher BA
Title Sabotage and exploitation in macrophages parasitized by intracellular protozoans.
Journal Reference Authors Denkers EY
Title From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii.
Journal Reference Authors Pollard AM, Knoll LJ, Mordue DG
Title The role of specific Toxoplasma gondii molecules in manipulation of innate immunity.
Journal Reference Authors Leng J, Butcher BA, Denkers EY
Title Dysregulation of macrophage signal transduction by Toxoplasma gondii: past progress and recent advances.
Journal Reference Authors Miller CM, Boulter NR, Ikin RJ, Smith NC
Title The immunobiology of the innate response to Toxoplasma gondii.
Journal Reference 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 Reference Authors Gazzinelli RT, Denkers EY
Title Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism.
Journal Reference Authors Lang C, Gross U, Luder CG
Title Subversion of innate and adaptive immune responses by Toxoplasma gondii.
Journal Reference Authors Blader IJ, Saeij JP
Title Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence.
Journal Reference Authors Boothroyd JC, Dubremetz JF
Title Kiss and spit: the dual roles of Toxoplasma rhoptries.
Journal Reference 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 Reference Authors Yarovinsky F
Title Toll-like receptors and their role in host resistance to Toxoplasma gondii.
Journal Reference Authors Coppens I, Joiner KA
Title Parasitehost cell interactions in toxoplasmosis: new avenues for intervention?
Journal Reference 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 Reference 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 Reference 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 Reference Authors Laliberte J, Carruthers VB
Title Host cell manipulation by the human pathogen Toxoplasma gondii.
Journal Reference Authors Bogdan C, Rollinghoff M
Title How do protozoan parasites survive inside macrophages?
Journal Reference 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 Related ko00590 Arachidonic acid metabolism
ko04620 Toll-like receptor signaling pathway
