DNA Sensor CGAS-mediated Immune Recognition

Overview

Journal Protein Cell

Publisher Oxford University Press

Specialties Biochemistry
Cell Biology

Date 2016 Oct 4

PMID 27696330

Citations 71

Authors

Pengyan Xia

Shuo Wang

Pu Gao

Guangxia Gao

Zusen Fan

Affiliations

Soon will be listed here.

Abstract

The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.

Citing Articles

The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer's disease.

Quan S, Fu X, Cai H, Ren Z, Xu Y, Jia L Mol Neurodegener. 2025; 20(1):25.

PMID: 40038765 PMC: 11877805. DOI: 10.1186/s13024-025-00815-2.

Bidirectional regulation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma.

Nie A, Xiao Z, Deng J, Li N, Hao L, Li S World J Gastrointest Oncol. 2025; 17(2):98556.

PMID: 39958554 PMC: 11755995. DOI: 10.4251/wjgo.v17.i2.98556.

Dual-tDCS Ameliorates Cerebral Injury and Promotes Motor Function Recovery via cGAS-STING Signaling Pathway in a Rat Model of Ischemic Stroke.

Huang J, Bao C, Yang C, Qu Y Mol Neurobiol. 2024; 62(4):4484-4498.

PMID: 39455539 DOI: 10.1007/s12035-024-04574-x.

Small molecule innate immune modulators in cancer therapy.

Goswami A, Goyal S, Khurana P, Singh K, Deb B, Kulkarni A Front Immunol. 2024; 15:1395655.

PMID: 39318624 PMC: 11419979. DOI: 10.3389/fimmu.2024.1395655.

Multifaceted activation of STING axis upon Nipah and measles virus-induced syncytia formation.

Amurri L, Dumont C, Pelissier R, Reynard O, Mathieu C, Spanier J PLoS Pathog. 2024; 20(9):e1012569.

PMID: 39283943 PMC: 11426520. DOI: 10.1371/journal.ppat.1012569.

References

Crow Y, Chase D, Lowenstein Schmidt J, Szynkiewicz M, Forte G, Gornall H . Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015; 167A(2):296-312. PMC: 4382202. DOI: 10.1002/ajmg.a.36887. View

Auerbuch V, Brockstedt D, Meyer-Morse N, ORiordan M, Portnoy D . Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J Exp Med. 2004; 200(4):527-33. PMC: 2211930. DOI: 10.1084/jem.20040976. View

Wu J, Chen Z . Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol. 2014; 32:461-88. DOI: 10.1146/annurev-immunol-032713-120156. View

Poltorak A, He X, Smirnova I, Liu M, Van Huffel C, Du X . Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998; 282(5396):2085-8. DOI: 10.1126/science.282.5396.2085. View

Yang P, An H, Liu X, Wen M, Zheng Y, Rui Y . The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway. Nat Immunol. 2010; 11(6):487-94. DOI: 10.1038/ni.1876. View

Civril F, Deimling T, de Oliveira Mann C, Ablasser A, Moldt M, Witte G . Structural mechanism of cytosolic DNA sensing by cGAS. Nature. 2013; 498(7454):332-7. PMC: 3768140. DOI: 10.1038/nature12305. View

Gay N, Symmons M, Gangloff M, Bryant C . Assembly and localization of Toll-like receptor signalling complexes. Nat Rev Immunol. 2014; 14(8):546-58. DOI: 10.1038/nri3713. View

Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H . A Toll-like receptor recognizes bacterial DNA. Nature. 2000; 408(6813):740-5. DOI: 10.1038/35047123. View

Schoggins J, Rice C . Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol. 2012; 1(6):519-25. PMC: 3274382. DOI: 10.1016/j.coviro.2011.10.008. View

10.

Saito T, Gale Jr M . Principles of intracellular viral recognition. Curr Opin Immunol. 2006; 19(1):17-23. DOI: 10.1016/j.coi.2006.11.003. View

11.

Gajewski T, Woo S, Zha Y, Spaapen R, Zheng Y, Corrales L . Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol. 2013; 25(2):268-76. DOI: 10.1016/j.coi.2013.02.009. View

12.

Wassermann R, Gulen M, Sala C, Perin S, Lou Y, Rybniker J . Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1. Cell Host Microbe. 2015; 17(6):799-810. DOI: 10.1016/j.chom.2015.05.003. View

13.

Zhang X, Brann T, Zhou M, Yang J, Oguariri R, Lidie K . Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN. J Immunol. 2011; 186(8):4541-5. PMC: 3720676. DOI: 10.4049/jimmunol.1003389. View

14.

Orzalli M, Broekema N, Diner B, Hancks D, Elde N, Cristea I . cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection. Proc Natl Acad Sci U S A. 2015; 112(14):E1773-81. PMC: 4394261. DOI: 10.1073/pnas.1424637112. View

15.

Chiu Y, MacMillan J, Chen Z . RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009; 138(3):576-91. PMC: 2747301. DOI: 10.1016/j.cell.2009.06.015. View

16.

Li Y, Chen R, Zhou Q, Xu Z, Li C, Wang S . LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection. Proc Natl Acad Sci U S A. 2012; 109(29):11770-5. PMC: 3406844. DOI: 10.1073/pnas.1203405109. View

17.

van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J . M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. 2007; 129(7):1287-98. DOI: 10.1016/j.cell.2007.05.059. View

18.

Sampson T, Saroj S, Llewellyn A, Tzeng Y, Weiss D . A CRISPR/Cas system mediates bacterial innate immune evasion and virulence. Nature. 2013; 497(7448):254-7. PMC: 3651764. DOI: 10.1038/nature12048. View

19.

Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu Y . The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol. 2011; 12(10):959-65. PMC: 3671854. DOI: 10.1038/ni.2091. View

20.

Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C, Hurbain I . The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity. 2013; 39(6):1132-42. DOI: 10.1016/j.immuni.2013.11.002. View