Human microglia and astrocytes express cGAS-STING viral sensing components. (29th September 2017)

• Record Type: Journal Article
• Authors: Jeffries, Austin M.; Marriott, Ian
• Is Part Of: Neuroscience letters. Volume 658(2017)
• Page Start: 53
• Page End: 56
• Publication Date: 2017-09-29
• Subjects: AMP adenosine monophosphate -- ATCC American type tissue collection -- ANOVA analysis of variance -- BDNA B-form DNA -- CNS central nervous system -- cDNA complementary DNA -- cGAS cyclic GMP-AMP synthase -- DAI DNA-dependent activator of interferon-regulatory factors -- DNA deoxyribonucleic acid -- dsDNA double stranded DNA -- ELISA enzyme linked immunosorbent assay -- FBS fetal bovine serum -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- GFAP glial fibrillary acidic protein -- GMP guanine monophosphate -- HSV-1 herpes simplex virus-1 -- IFN interferon -- IRF3 interferon regulatory factor 3 -- L2K lipofectamine 2000 -- mRNA messenger ribonucleic acid -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- RIG-I retinoic acid-inducible gene-I -- RNA ribonucleic acid -- RT-PCR reverse transcribed polymerase chain reaction -- SEM standard error of the mean -- STING stimulator of interferon genes -- TERT telomerase reverse transcriptase -- TBK1 TANK binding kinase 1 -- VSV vesicular stomatitis virus; Human -- Microglia -- Astrocytes -- cyclic GMP-AMP synthase -- Nucleic acid sensing; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.08.039
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Primary and immortalized human microglia and astrocytes are responsive to foreign intracellular double stranded DNA. Human microglia and astrocytes show robust expression of cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), at rest and after activation. Human microglia and astrocytes constitutively express the critical downstream cGAS adaptor protein, stimulator of interferon genes (STING). Abstract: While microglia and astrocytes are known to produce key inflammatory and anti-viral mediators following infection with replicative DNA viruses, the mechanisms by which these cell types perceive such threats are poorly understood. Recently, cyclic GMP-AMP synthase (cGAS) has been identified as an important cytosolic sensor for DNA viruses and retroviruses in peripheral leukocytes. Here we confirm the ability of human microglial and astrocytic cell lines and primary human glia to respond to foreign intracellular double stranded DNA. Importantly, we provide the first demonstration that human microglia and astrocytes show robust levels of cGAS protein expression at rest and following activation. Furthermore, we show these cell types also constitutively express the critical downstream cGAS adaptor protein, stimulator of interferon genes (STING). The present finding that human glia express the principle components of the cGAS-STING pathway provides a foundation for future studies to investigate the relative importance of these molecules in clinically relevant viral CNS infections.