Dual regulation of osteopontin production by TLR stimulation in dendritic cells

Abstract

Event Abstract Back to Event Dual regulation of osteopontin production by TLR stimulation in dendritic cells Tiziana Musso1* 1 University of Torino, Department of Public Health and Pediatric Sciences, Italy Osteopontin (OPN), a cytokine produced, among others, by dendritic cells (DC), is involved in inflammation and defence against pathogens. Here we report that the activation of the MyD88 pathway by TLR2, TLR5 and TLR7/8 agonists, or IL-1β, induces high levels of OPN in human DC. Conversely, LPS and Poly I:C, two TLR3 and TLR4 agonists that engage the TRIF pathway, were ineffective. TLR2 agonists were the strongest OPN inducers, and OPN production was highly stimulated by TLR2-triggering bacteria (S. aureus), but not by TLR4-triggering E. coli. Co-stimulation experiments revealed that TLR3 and TLR4 agonists, beyond being inactive by themselves, sharply limited TLR2-dependent OPN production, by activating a TRIF-dependent inhibition of the MyD88-dependent OPN production. MyD88 silencing impaired TLR2-dependent OPN induction, whereas TRIF pathway blockage by chloroquine, dynasore or TRIF knockdown prevented the TLR3/4 agonist-mediated inhibition, which was independent from the endogenous production of type I IFN, IL-29, IL-10 or TGF-β. LPS and Poly I:C inhibitory activity was associated with the release of a >10 kDa protein factor(s). We also demonstrated that the higher OPN levels produced by S. aureus-treated DC, compared to E. coli-treated DC, were responsible for a markedly increased production of IL-17 by CD4+ T cells. These results highlight the biological relevance of the differential OPN induction by TLR2 and TLR4 agonists, and emphasize the importance of TLR cross-talk in OPN induction. This implies that OPN regulation by TLR signaling is critical in shaping inflammatory responses, and may modulate IL-17 production in response to pathogens. Keywords: Osteopontin, TLRs (Toll-like receptors), DC, IL17A, Bacteria Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Musso T (2013). Dual regulation of osteopontin production by TLR stimulation in dendritic cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00760 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 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Tiziana Musso, University of Torino, Department of Public Health and Pediatric Sciences, Torino, 10126, Italy, tiziana.musso@unito.it 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 Tiziana Musso Google Tiziana Musso Google Scholar Tiziana Musso PubMed Tiziana Musso 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.