Event Abstract Back to Event Carbon Monoxide Impairs Mitochondria-dependent Endosomal Maturation and Antigen Presentation in Dendritic Cells Sebastián A. Riquelme1, 2, Susan M. Bueno1, 2* and Alexis M. Kalergis1, 2, 3* 1 Millenium Institute of Immunology and Immunotherapy Pontificia Universidad Católica de Chile, Chile 2 Inserm U1064, France 3 Faculty of Rheumatology Pontificia Universidad Católica de Chile, Chile Heme-oxygenase 1 (HO-1) prevents the host from T cell-mediated inflammatory diseases by producing carbon monoxide (CO) and impairing dendritic cells (DCs) immunogenicity. However, the cellular mechanisms that cause this inhibition remain unknown. Here we show that CO impairs mitochondrial function in DCs by reducing both the mitochondrial membrane potential and ATP production, resembling the effect of a non-lethal dose of a classical mitochondria uncoupler (CCCP). Furthermore, both CO and CCCP reduced cargo transport, endosome-to-lysosome fusion and antigen processing dampening the production of peptide-MHC complexes on the surface of DCs. As a result, inhibition of naive CD4+ T cell priming was observed. Furthermore, both uncoupling molecules also significantly reduced CD8+ T cell-dependent type 1 diabetes onset in vivo. These results showed for the first time that CO interferes with T cell priming by blocking an unknown mitochondria-dependent antigen-processing pathway in mature DC. Interestingly, other immune functions in uncoupled DCs, such as antigen capture, cytokine secretion, co-stimulation and cell survival relied on glycolysis, suggesting that oxidative phosphorylation might only play a key role for the maturation of antigen-containing endosomes. Therefore, mitochondrial shutdown could be considered for DCs-based therapies to prevent antigen-specific T cell-mediated inflammatory pathologies. Acknowledgements This work was supported by funding from the Millennium Institute on Immunology and Immunotherapy from Chile (P09/016-F to AMK), La Région Pays de la Loire through the “Chaire d’excellence” program to AMK and Grant “Nouvelles Equipes-nouvelles thématiques” (AK), INSERM CDD grant, the ECOS France-Chile grant, FONDECYT no 1070352, FONDECYT no 1050979, FONDECYT no 1040349, FONDECYT no 1100926, FONDECYT no 1110397, FONDECYT no 1100971, FONDECYT no 1110604 and BMRC CTU06. Keywords: Carbon Monoxide, Heme Oxygenase-1, Dendritic Cells, Mitochondria, Antigen Presentation, tolerance Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Oral Presentation Topic: Innate Immunity Citation: Riquelme SA, Bueno SM and Kalergis AM (2015). Carbon Monoxide Impairs Mitochondria-dependent Endosomal Maturation and Antigen Presentation in Dendritic Cells. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00279 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: 04 May 2015; Published Online: 15 Sep 2015. * Correspondence: Dr. Susan M Bueno, Millenium Institute of Immunology and Immunotherapy Pontificia Universidad Católica de Chile, Santiago, Chile, sbueno@bio.puc.cl Dr. Alexis M Kalergis, Millenium Institute of Immunology and Immunotherapy Pontificia Universidad Católica de Chile, Santiago, Chile, akalergis@bio.puc.cl 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 Sebastián A Riquelme Susan M Bueno Alexis M Kalergis Google Sebastián A Riquelme Susan M Bueno Alexis M Kalergis Google Scholar Sebastián A Riquelme Susan M Bueno Alexis M Kalergis PubMed Sebastián A Riquelme Susan M Bueno Alexis M Kalergis 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.