Expression and functional analysis of nucleic acid sensors in astrocytes and microglia

Abstract

Event Abstract Back to Event Expression and functional analysis of nucleic acid sensors in astrocytes and microglia Donal J. Cox1*, Robert H. Field2, David G. Williams1, Marcin Baran3, Andrew G. Bowie3, Colm Cunningham4 and Aisling Dunne1 1 Trinity College Dublin, School of Biochemistry and Immunology, Ireland 2 Newcastle University Medical, United Kingdom 3 Trinity College Dublin, School of Biochemistry and Immunology, Ireland 4 Trinity College Dublin, School of Biochemistry and Immunology & Trinity College Institute of Neuroscience, Ireland The recognition of nucleic acids is essential in combating viral and bacterial pathogens. The sensors and pathways involved in RNA/DNA detection have only recently been discovered and have expanded over the last number of years. TLR9 was the first DNA sensor to be discovered followed by the cytosolic DNA receptors which include members of the PYHIN family, DAI and the enzyme cyclic GMP-AMP synthase (cGAS). The PYHIN family are so called as they contain an N-terminal PYRIN domain and a C-terminal HIN domain. These proteins bind DNA directly via their HIN domains culminating in the production of anti-viral and pro-inflammatory cytokines. Microglia and astrocytes can respond to cytosolic poly(I:C), via RIG-like receptors, however the contribution of DNA sensors has not been fully explored in neuroimmune cells. Furthermore, the contribution of individual cell types, in particular astrocytes, has been confounded by difficulties in obtaining pure populations devoid of contaminating microglia. Finally, most studies reported to date have used poly(dA:dT) as a DNA mimetic, however this can be reverse transcribed to RNA by RNA pol III and is capable of activating RNA sensors. We have carried out extensive expression profiling of the newly described DNA sensors in purified astrocytes and microglia and have found that both cell types have the capacity to induce a strong anti-viral response in the presence of immune stimulatory DNA and RNA. Furthermore we have found that key sensors are upregulated in a murine model of neurodegeneration and this is dependent on the type I interferon, IFN-β. Acknowledgements This research was carried out with the support of the Wellcome Trust and the Programme for Research in Third Level Institutions (PRTLI), which is co-funded by the European Regional Development Fund and the HEA. Keywords: Nucleic acid sensing, Microglia, Astrocytes, type I interferon, neurodegeneration Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Poster Presentation Topic: Early Career Neuroscience Citation: Cox DJ, Field RH, Williams DG, Baran M, Bowie AG, Cunningham C and Dunne A (2014). Expression and functional analysis of nucleic acid sensors in astrocytes and microglia. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00039 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Sep 2014; Published Online: 18 Sep 2014. * Correspondence: Mr. Donal J Cox, Trinity College Dublin, School of Biochemistry and Immunology, Dublin 2, Ireland, coxdo@tcd.ie Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Donal J Cox Robert H Field David G Williams Marcin Baran Andrew G Bowie Colm Cunningham Aisling Dunne Google Donal J Cox Robert H Field David G Williams Marcin Baran Andrew G Bowie Colm Cunningham Aisling Dunne Google Scholar Donal J Cox Robert H Field David G Williams Marcin Baran Andrew G Bowie Colm Cunningham Aisling Dunne PubMed Donal J Cox Robert H Field David G Williams Marcin Baran Andrew G Bowie Colm Cunningham Aisling Dunne Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.