Double-stranded RNA (dsRNA)-induced IP-10/CXCL-10 production is augmented by Fas activation

Abstract

Event Abstract Back to Event Double-stranded RNA (dsRNA)-induced IP-10/CXCL-10 production is augmented by Fas activation Caitriona Lyons1, Rachael Moran2, Aileen Houston3 and Elizabeth Brint1* 1 University College Cork (UCC), Pathology, Ireland 2 University College Cork, Ireland 3 University College Cork, Medicine, Ireland Viral double-stranded RNA (dsRNA) is recognised by Pathogen Recognition Receptors (PRRs) including RIGI-like Receptors (RLRs) and Toll-Like Receptors (TLRs) and results in cytokine/chemokine production. Fas, a well characterised death receptor, may also mediate inflammation. Our aim was to investigate potential crosstalk between the Fas signalling pathway and anti-viral signalling pathways. THP-1 monocyte-derived macrophages (THP1-Mø’s) were stimulated with poly(I:C) (dsRNA mimetic) +/-agonistic anti-Fas antibody (CH-11). Co-stimulation resulted in a 50% reduction in IL-8, TNFα, IFNβ and IL-10, relative to poly(I:C) alone, as assessed by qRT-PCR. In contrast, IP-10/CXCL-10 production increased by 50% following co-stimulation relative to poly(I:C) alone. Results were confirmed using human monocyte-derived macrophages. Fas-associated death domain (FADD) is recruited to Fas following Fas activation and is required for Fas signalling. Overexpression of FADD inhibited poly(I:C)-induced IP-10 luciferase production, while inhibiting FADD signalling by overexpressing the FADD death-domain augmented poly(I:C)-induced IP-10 luciferase. To further confirm the role of FADD in poly(I:C)-induced IP-10/CXCL-10 production, wild-type and FADD-/-MEFs were treated with increasing doses of poly(I:C). IP-10/CXCL-10 production in FADD-/-MEFs was increased compared to wild-type MEFs. Our results indicate that activation of the Fas signalling pathway, may be necessary for optimal poly(I:C) induced IP-10/CXCL-10 production. As IP-10/CXCL-10 is a potent T-cell chemo-attractant, cross-talk between these pathways may potentially promote the recruitment of T-cells to sites of viral infection. Acknowledgements Science Foundation Ireland (SFI) Dr. Liam Fanning, Molecular Virology, Department of Medicine, Clinical Sciences Building (UCC), Cork University Hospital, Cork, Ireland Keywords: Fas, IP-10, CXCL-10, dsRNA, THP-1 macrophages Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Lyons C, Moran R, Houston A and Brint E (2013). Double-stranded RNA (dsRNA)-induced IP-10/CXCL-10 production is augmented by Fas activation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00541 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: 29 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Elizabeth Brint, University College Cork (UCC), Pathology, Cork, Ireland, e.brint@ucc.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 Caitriona Lyons Rachael Moran Aileen Houston Elizabeth Brint Google Caitriona Lyons Rachael Moran Aileen Houston Elizabeth Brint Google Scholar Caitriona Lyons Rachael Moran Aileen Houston Elizabeth Brint PubMed Caitriona Lyons Rachael Moran Aileen Houston Elizabeth Brint 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.