Specific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified sensor of cytosolic DNA which activates the IRF and NF-{kappa}B transcription factors, leading to production of type I interferon and other cytokines. The second type of cytoplasmic DNA sensor is AIM2. Upon sensing DNA, AIM2 triggers the assembly of the inflammasome, culminating in interleukin maturation. In addition to these receptors, there is a mechanism to sense foreign DNA, with the host RNA polymerase III converting the DNA into RNA for recognition by the RNA sensor RIG-I. These pathways provide various means to alert the cell.

Organismal Systems; Immune system
BRITE hierarchy

PMID:19362700

Yanai H, Savitsky D, Tamura T, Taniguchi T

Regulation of the cytosolic DNA-sensing system in innate immunity: a current view.

Curr Opin Immunol 21:17-22 (2009)
DOI:10.1016/j.coi.2009.01.005

PMID:19497760

Vilaysane A, Muruve DA

The innate immune response to DNA.

Semin Immunol 21:208-14 (2009)
DOI:10.1016/j.smim.2009.05.006

PMID:18573338

Takeshita F, Ishii KJ

Intracellular DNA sensors in immunity.

Curr Opin Immunol 20:383-8 (2008)
DOI:10.1016/j.coi.2008.05.009

PMID:19122387

Takaoka A, Shinohara S

DNA sensors in innate immune system.

Uirusu 58:37-46 (2008)
DOI:10.2222/jsv.58.37

PMID:18280611

Takaoka A, Taniguchi T

Cytosolic DNA recognition for triggering innate immune responses.

Adv Drug Deliv Rev 60:847-57 (2008)
DOI:10.1016/j.addr.2007.12.002

PMID:18941233

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 181:6427-34 (2008)
DOI:10.4049/jimmunol.181.9.6427

PMID:19590578

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 10:916-22 (2009)
DOI:10.1038/embor.2009.109

PMID:18375758

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 105:5477-82 (2008)
DOI:10.1073/pnas.0801295105

PMID:18724932

Stetson DB, Ko JS, Heidmann T, Medzhitov R

Trex1 prevents cell-intrinsic initiation of autoimmunity.

Cell 134:587-98 (2008)
DOI:10.1016/j.cell.2008.06.032

PMID:19321146

Schroder K, Muruve DA, Tschopp J

Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.

Curr Biol 19:R262-5 (2009)
DOI:10.1016/j.cub.2009.02.011

PMID:19567913

Krieg AM

AIMing 2 detect foreign DNA.

Sci Signal 2:pe39 (2009)
DOI:10.1126/scisignal.277pe39

PMID:19665965

O'Neill LA

DNA makes RNA makes innate immunity.

Cell 138:428-30 (2009)
DOI:10.1016/j.cell.2009.07.021

PMID:16286919

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 7:40-8 (2006)
DOI:10.1038/ni1282

PMID:19767723

Cao X

New DNA-sensing pathway feeds RIG-I with RNA.

Nat Immunol 10:1049-51 (2009)
DOI:10.1038/ni1009-1049

PMID:23258413

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 339:786-91 (2013)
DOI:10.1126/science.1232458