Cytosolic DNA-sensing pathway (Homo sapiens)

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1-15NucleusInflammasomeVaccinia virusPyroptosisOligomerizationProinflammatorycytokine processingDNA polymerase III5'-ppp-dsRNAcGAMPPOLR3CPOLR2EPOLR3GPOLR3DPOLR2LPOLR3FPOLR2KPOLR3GLPOLR3KPOLR1DPOLR3BPOLR3HPOLR2FPOLR1CdsDNAPOLR3APOLR3ETREX1POLR2HADARZBP1RIPK1RIPK3IKBKGIKBKBCHUKNFKB1RELANFKB1RELANFKBIANFKBIBPNFKBIAPNFKBIBUbiquitin-mediated proteolysisPro-inflammatory cytokines / chemokinesNFKB1RELAIL6CCL4L2CCL5CXCL10AIM2CASP1PYCARDIL1BIL18IL33Listeria monocytogenesLegionella pneumophilaShigella FlexneriEnteropathic E.coliHost cellsAdenovirusHerpes simplex virus 1Epstein-Barr virusLegionella pneumophiladsDNAIRF3IRF7IRF3IRF7Type I interferonsIFNA10IFNA8IFNA16IFNA2IFNA7IFNA21IFNA17IFNA14IFNA4IFNA1IFNA13IFNA5IFNA6IFNB1OligomerizationTBK1IKBKECGASDDX58TRIM25CYLDRNF125ISG15ATG5ATG12NLRX1MAVSTMEM173TRADDFADDRIPK1CASP8CASP10CCL4


Description

As part of the innate immune system, specific cytosolic pattern recognition receptors recognize DNA from invading viruses and bacteria. These receptors have specificity for certain pathogens.

The three receptors that recognize double-stranded cytosolic DNA are CGAS (GMP-AMP Synthase), ZBP1 (DAI) and AIM. CGAS signals via STING (TREM173) and eventually results in expression of type I interferons. ZBP1 activates NFkb and IRF transcription factors which results in expression of interferons and cytokines/chemokines. Activation of AIM leads to the formation of the inflammasome complex, which activates caspase-1 and triggers a form of apoptosis known as pyroptosis.

In addition to sensors that directly detect DNA, another mechanism exists where the foreign DNA is first translated into RNA by host polymerase. The RNA is then recognized by the RNA sensor RIG-I, which leads to NFkb and IRF activation.

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Ontology Terms

 

Bibliography

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  1. Yanai H, Savitsky D, Tamura T, Taniguchi T; ''Regulation of the cytosolic DNA-sensing system in innate immunity: a current view.''; Curr Opin Immunol, 2009 PubMed Europe PMC
  2. Vilaysane A, Muruve DA; ''The innate immune response to DNA.''; Semin Immunol, 2009 PubMed Europe PMC
  3. Takeshita F, Ishii KJ; ''Intracellular DNA sensors in immunity.''; Curr Opin Immunol, 2008 PubMed Europe PMC
  4. Takaoka A, Shinohara S; ''DNA sensors in innate immune system.''; Uirusu, 2008 PubMed Europe PMC
  5. Takaoka A, Taniguchi T; ''Cytosolic DNA recognition for triggering innate immune responses.''; Adv Drug Deliv Rev, 2008 PubMed Europe PMC
  6. Kaiser WJ, Upton JW, Mocarski ES; ''Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors.''; J Immunol, 2008 PubMed Europe PMC
  7. Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, Vazquez J, Benedict CA, Tschopp J; ''DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.''; EMBO Rep, 2009 PubMed Europe PMC
  8. Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T; ''Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC
  9. Stetson DB, Ko JS, Heidmann T, Medzhitov R; ''Trex1 prevents cell-intrinsic initiation of autoimmunity.''; Cell, 2008 PubMed Europe PMC
  10. Schroder K, Muruve DA, Tschopp J; ''Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.''; Curr Biol, 2009 PubMed Europe PMC
  11. Krieg AM; ''AIMing 2 detect foreign DNA.''; Sci Signal, 2009 PubMed Europe PMC
  12. O'Neill LA; ''DNA makes RNA makes innate immunity.''; Cell, 2009 PubMed Europe PMC
  13. Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H, Sato S, Yamamoto M, Uematsu S, Kawai T, Takeuchi O, Akira S; ''A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA.''; Nat Immunol, 2006 PubMed Europe PMC
  14. Cao X; ''New DNA-sensing pathway feeds RIG-I with RNA.''; Nat Immunol, 2009 PubMed Europe PMC
  15. Sun L, Wu J, Du F, Chen X, Chen ZJ; ''Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.''; Science, 2013 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
105163view20:48, 15 July 2019KhanspersAdded lit refs
104945view17:10, 26 June 2019KhanspersModified description
104902view21:47, 23 June 2019EgonwReplaced a secondary ChEBI identifier with a primary identifier.
104878view00:31, 22 June 2019KhanspersModified description
104877view00:28, 22 June 2019KhanspersOntology Term : 'bacterial infectious disease' added !
104876view00:28, 22 June 2019KhanspersOntology Term : 'viral infectious disease' added !
104875view00:28, 22 June 2019KhanspersOntology Term : 'pattern recognition receptor mediated signaling pathway' added !
104874view00:27, 22 June 2019KhanspersOntology Term : 'PW:0000816' removed !
104873view00:27, 22 June 2019KhanspersOntology Term : 'signaling pathway' added !
104872view00:27, 22 June 2019KhanspersOntology Term : 'Retinoic acid-inducible gene (RIG) I-like receptor signaling pathway' added !
104871view00:24, 22 June 2019Khansperscorrected complexes etc
104870view00:04, 22 June 2019KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
5'-ppp-dsRNAGeneProduct
ADARGeneProductENSG00000160710 (Ensembl)
AIM2GeneProductENSG00000163568 (Ensembl)
ATG12GeneProductENSG00000145782 (Ensembl)
ATG5GeneProductENSG00000057663 (Ensembl)
CASP10GeneProductENSG00000003400 (Ensembl)
CASP1GeneProductENSG00000137752 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CCL4GeneProductENSG00000275302 (Ensembl)
CCL4L2GeneProductENSG00000276070 (Ensembl)
CCL5GeneProductENSG00000271503 (Ensembl)
CGASGeneProductENSG00000164430 (Ensembl)
CHUKGeneProductENSG00000213341 (Ensembl)
CXCL10GeneProductENSG00000169245 (Ensembl)
CYLDGeneProductENSG00000083799 (Ensembl)
DDX58GeneProductENSG00000107201 (Ensembl)
FADDGeneProductENSG00000168040 (Ensembl)
IFNA10GeneProduct3446 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA13GeneProduct3447 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA1GeneProduct3439 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA14GeneProduct3448 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA16GeneProduct3449 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA17GeneProduct3451 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA21GeneProduct3452 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA2GeneProduct3440 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA4GeneProduct3441 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA5GeneProduct3442 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA6GeneProduct3443 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA7GeneProduct3444 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNA8GeneProduct3445 (Entrez Gene) Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNB1GeneProduct3456 (Entrez Gene) Original kegg element: gene;1;hsa:3456
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKEGeneProductENSG00000263528 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
IL18GeneProductENSG00000150782 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL33GeneProductENSG00000137033 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
IRF3GeneProductENSG00000126456 (Ensembl)
IRF7GeneProductENSG00000185507 (Ensembl)
ISG15GeneProductENSG00000187608 (Ensembl)
MAVSGeneProductENSG00000088888 (Ensembl)
NFKB1GeneProduct4790 (Entrez Gene)
NFKBIAGeneProductENSG00000100906 (Ensembl)
NFKBIBGeneProductENSG00000104825 (Ensembl)
NLRX1GeneProductENSG00000160703 (Ensembl)
POLR1CGeneProductENSG00000171453 (Ensembl)
POLR1DGeneProductENSG00000186184 (Ensembl)
POLR2EGeneProductENSG00000099817 (Ensembl)
POLR2FGeneProductENSG00000100142 (Ensembl)
POLR2HGeneProductENSG00000163882 (Ensembl)
POLR2KGeneProductENSG00000147669 (Ensembl)
POLR2LGeneProductENSG00000177700 (Ensembl)
POLR3AGeneProductENSG00000148606 (Ensembl)
POLR3BGeneProductENSG00000013503 (Ensembl)
POLR3CGeneProductENSG00000186141 (Ensembl)
POLR3DGeneProductENSG00000168495 (Ensembl)
POLR3EGeneProductENSG00000058600 (Ensembl)
POLR3FGeneProductENSG00000132664 (Ensembl)
POLR3GGeneProductENSG00000113356 (Ensembl)
POLR3GLGeneProductENSG00000121851 (Ensembl)
POLR3HGeneProductENSG00000100413 (Ensembl)
POLR3KGeneProductENSG00000161980 (Ensembl)
PYCARDGeneProductENSG00000103490 (Ensembl)
PyroptosisPathway
RELAGeneProductENSG00000173039 (Ensembl)
RIPK1GeneProductENSG00000137275 (Ensembl)
RIPK3GeneProductENSG00000129465 (Ensembl)
RNF125GeneProductENSG00000101695 (Ensembl)
TBK1GeneProductENSG00000183735 (Ensembl)
TMEM173GeneProductENSG00000184584 (Ensembl)
TRADDGeneProductENSG00000102871 (Ensembl)
TREX1GeneProductENSG00000213689 (Ensembl)
TRIM25GeneProductENSG00000121060 (Ensembl)
Ubiquitin-mediated proteolysisPathwayWP183 (WikiPathways)
ZBP1GeneProductENSG00000124256 (Ensembl)
cGAMPMetaboliteCHEBI:71580 (ChEBI)
dsDNAMetaboliteCHEBI:16991 (ChEBI)

Annotated Interactions

No annotated interactions

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