Event Abstract Back to Event Immunomodulatory effects of HIV-1 gp120 on human dendritic cells: role of STAT3/IL-6 axis Manuela Del Cornò1, Gloria Donninelli1, Barbara Varano1, Andrea Masotti2, Letizia Da Sacco2 and Sandra Gessani1* 1 Istituto Superiore di Sanità, Italy 2 Bambino Gesù Children's Hospital, Italy The ability of HIV-1 to exploit the host immune responses to its own advantage is critical in the pathogenesis of AIDS. Since dendritic cells (DCs) are key players in the induction of immune responses, the modulation of their functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to recombinant gp120 transcriptionally activates IL-6 expression and promotes its secretion in a concentration and time-dependent manner. Activation of MAPK p38 is involved in gp120 triggered IL-6 over-expression as p38 specific inhibitors markedly reduced IL-6 secretion. IL-6 over-expression induces at later time points accumulation of the tyrosine phosphorylated form of STAT3. Blocking IL-6 biological activity resulted in a dramatic reduction of STAT3 activation suggesting that gp120 might interfere with the STAT3/IL-6 axis. Consistently with this hypothesis, blocking STAT3 activation markedly decreases IL-6 secretion. Reconstruction of the signaling pathway triggered by gp120 in MDDCs unraveled a biphasic activation of STAT3, triggered early on by gp120 and leading to IL-6 secretion which, at later time points, induces a second round of STAT3 activation. Moreover, the possible involvement of cellular microRNAs in the regulation of this process will be discussed. Overall, these results indicate that DCs may contribute to the up-modulation of IL-6 found in HIV infected individuals. Furthermore, chronic activation of STAT3 in DCs may provide an explanation for the impairment of DC functions. Acknowledgements This work was supported by a grant from the Italian Ministry of Health, Bando Nazionale AIDS 2009-2010, 3H/31 to SG Keywords: Dendritic Cells, HIV-1, stat3, IL-6, signaling Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Del Cornò M, Donninelli G, Varano B, Masotti A, Da Sacco L and Gessani S (2013). Immunomodulatory effects of HIV-1 gp120 on human dendritic cells: role of STAT3/IL-6 axis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00928 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: 27 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Sandra Gessani, Istituto Superiore di Sanità, Rome, Italy, sandra.gessani@iss.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 Manuela Del Cornò Gloria Donninelli Barbara Varano Andrea Masotti Letizia Da Sacco Sandra Gessani Google Manuela Del Cornò Gloria Donninelli Barbara Varano Andrea Masotti Letizia Da Sacco Sandra Gessani Google Scholar Manuela Del Cornò Gloria Donninelli Barbara Varano Andrea Masotti Letizia Da Sacco Sandra Gessani PubMed Manuela Del Cornò Gloria Donninelli Barbara Varano Andrea Masotti Letizia Da Sacco Sandra Gessani 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.