Autophagy inducing drugs contribute to control Mycobacterium tuberculosis infection

Abstract

Event Abstract Back to Event Autophagy inducing drugs contribute to control Mycobacterium tuberculosis infection Esmeralda Juárez1*, Claudia Carranza1, Guadalupe Sánchez1, Mitzi González1, Jaime Chávez2, Martha Torres1 and Eduardo Sada1 1 National Institute of Respiratory Diseases, Research in Microbiology, Mexico 2 National Institute of Respiratory Diseases, Research in Bronchial Hyperreactivity, Mexico Tuberculosis is a major cause of morbidity and mortality in the world today. M. tuberculosis (Mtb) escapes from macrophages bactericidal responses. Autophagy is a complex process that ultimately generates a degradative vesicle called autophagosome that has been demonstrated to participate in the control of Mtb infection. Different drugs used for a variety of medical conditions can induce autophagy. In this study, we used an in vitro model of human monocyte derived macrophages (MDM) and primary murine alveolar macrophages (AM) that were infected with Mtb H37Rv and treated with rapamycin, loperamide, carbamazepine, verapamil and valproic acid 24h post-infection. We examined the induction of autophagy and the containment of Mtb within the autophagosomes by fluorescence microscopy, the gene expression of autophagy related proteins LC3 and ATG16L1 by real time PCR and the reduction in the intracellular Mtb burden by CFU. We found that rapamycin and valproic acid induced autophagy in 77.48 ± 13.29 and 88 ± 8.16 % of MDM, respectively, and in 70.62 ± 21.78 and 70 ± 6.83 % of AM, respectively, but did not improve Mtb growth control. Loperamide, carbamazepine and verapamil significantly induced autophagy in 70-90% of uninfected and infected human and murine macrophages and helped internalizing Mtb within autophagosomes; colocalization of Mtb with LC3 was larger than 60% in all treatments whereas in untreated cells it was of 34.73 ± 12.84 %. AM treated with carbamazepine, loperamide and verapamil decreased the intracellular bacillary burden up to 50% when administered in vitro. All drugs up-regulated the gene expression of LC3 and ATG16L1. To evaluate the capability of the drugs to pre-activate lung macrophages in vivo, we administered the three drugs intraperitoneally to uninfected mice, recovered the AM and infected them ex vivo. Loperamide treatment significantly reduced the intracellular growth of Mtb at Day 3 post infection without further treatment. Treatment with autophagy inducing-drugs has potential for use as adjunctive therapy in tuberculosis. Acknowledgements Funding: CONACYT-SALUD- 181008 Keywords: Autophagy, Macrophages, Tuberculosis, Loperamide, Carbamazepine 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: Poster Presentation Topic: Infectious and parasitic diseases Citation: Juárez E, Carranza C, Sánchez G, González M, Chávez J, Torres M and Sada E (2015). Autophagy inducing drugs contribute to control Mycobacterium tuberculosis infection. 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.2015.05.00160 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: 06 May 2015; Published Online: 14 Sep 2015. * Correspondence: Dr. Esmeralda Juárez, National Institute of Respiratory Diseases, Research in Microbiology, Mexico City, Federal District, 14080, Mexico, ejuarez@iner.gob.mx 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 Esmeralda Juárez Claudia Carranza Guadalupe Sánchez Mitzi González Jaime Chávez Martha Torres Eduardo Sada Google Esmeralda Juárez Claudia Carranza Guadalupe Sánchez Mitzi González Jaime Chávez Martha Torres Eduardo Sada Google Scholar Esmeralda Juárez Claudia Carranza Guadalupe Sánchez Mitzi González Jaime Chávez Martha Torres Eduardo Sada PubMed Esmeralda Juárez Claudia Carranza Guadalupe Sánchez Mitzi González Jaime Chávez Martha Torres Eduardo Sada 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.