Mycobacterium tuberculosis Inhibits MHC class II antigen presentation by blocking macro-autophagy through the PE_PGRS47 protein

Abstract

Event Abstract Back to Event Mycobacterium tuberculosis Inhibits MHC class II antigen presentation by blocking macro-autophagy through the PE_PGRS47 protein Andres Baena1*, Neeraj K. Saini2, Toni Ng2, Manjunatha Venkathaswamy2, Steven Kenedy2, Rafael Prados-Rosales2, John Chan2, William Jacobs2 and Steven A. Porcelli2 1 Universidad de Antioquia, Grupo de Inmunología Celular e Inmunogenética, Departamento de Microbiología y Parasitología, Colombia 2 Albert Einstein College of Medicine, United States Mycobacterium tuberculosis (Mtb) is a complex and successful pathogen that has been able to infect and persist in a large fraction of the human population as a result of multiple different strategies to evade host immune responses. A central mechanism of immune evasion by M. tuberculosis is the inhibition of MHC class II antigen presentation. Through a genome-wide screen using the transfer of Mtb cosmids to M.smegmatis, we identified six cosmids that inhibited MHC class II restricted antigen presentation by infected dendritic cells. Sequence analysis indicated partial overlap in the genes contained within several of the cosmids, indicating that most likely at least three different loci were involved in the suppression of MHC class II function. Four cosmids were found to encode genes that inhibited macro-autophagy by infected phagocytic cells, suggesting a likely mechanism for the suppression of MHC class II presentation. Detailed analysis of one cosmid, identified the gene PE_PGRS47 (Rv2741) to be both necessary and sufficient for inhibition of macro-autophagy, and for suppression of MHC class II function. Our findings demonstrated that a member of the PE_PGRS family of virulence-related proteins was able to inhibit autophagy, and that the inhibition was associated with alteration of calcium fluxes originating at the plasma membrane and the ER. These studies provides new insight into the virulence-related functions of the enigmatic PE_PGRS protein family, and gives further information on the mechanisms by which M. tuberculosis interferes with MHC class II presentation and CD4+ T cell responses. In addition, the results further emphasize on the importance of autophagy in the host immune response to intracellular pathogens. The identification of these specific immune evasion pathways can potentially provide a stronger rational basis for the development of improved vaccines to prevent or treat tuberculosis. Acknowledgements Programa de Sostenibilidad, Universidas de Antioquia 2014-2015 Keywords: Mycobacterium tuberculosis, Immune Evasion, Antigen Presentation, Authophagy, MHC class II 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: Infectious and parasitic diseases Citation: Baena A, Saini NK, Ng T, Venkathaswamy M, Kenedy S, Prados-Rosales R, Chan J, Jacobs W and Porcelli SA (2015). Mycobacterium tuberculosis Inhibits MHC class II antigen presentation by blocking macro-autophagy through the PE_PGRS47 protein. 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.2015.05.00326 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 Apr 2015; Published Online: 15 Sep 2015. * Correspondence: Mr. Andres Baena, Universidad de Antioquia, Grupo de Inmunología Celular e Inmunogenética, Departamento de Microbiología y Parasitología, Medellín, Colombia, andres.baenag@udea.edu.co 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 Andres Baena Neeraj K Saini Toni Ng Manjunatha Venkathaswamy Steven Kenedy Rafael Prados-Rosales John Chan William Jacobs Steven A Porcelli Google Andres Baena Neeraj K Saini Toni Ng Manjunatha Venkathaswamy Steven Kenedy Rafael Prados-Rosales John Chan William Jacobs Steven A Porcelli Google Scholar Andres Baena Neeraj K Saini Toni Ng Manjunatha Venkathaswamy Steven Kenedy Rafael Prados-Rosales John Chan William Jacobs Steven A Porcelli PubMed Andres Baena Neeraj K Saini Toni Ng Manjunatha Venkathaswamy Steven Kenedy Rafael Prados-Rosales John Chan William Jacobs Steven A Porcelli 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.