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Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death

It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a nov...

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Autores principales: Aporta, Adriana, Arbues, Ainhoa, Aguilo, Juan I., Monzon, Marta, Badiola, Juan J., de Martino, Alba, Ferrer, Nadia, Marinova, Dessislava, Anel, Alberto, Martin, Carlos, Pardo, Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446966/
https://www.ncbi.nlm.nih.gov/pubmed/23028853
http://dx.doi.org/10.1371/journal.pone.0045213
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author Aporta, Adriana
Arbues, Ainhoa
Aguilo, Juan I.
Monzon, Marta
Badiola, Juan J.
de Martino, Alba
Ferrer, Nadia
Marinova, Dessislava
Anel, Alberto
Martin, Carlos
Pardo, Julian
author_facet Aporta, Adriana
Arbues, Ainhoa
Aguilo, Juan I.
Monzon, Marta
Badiola, Juan J.
de Martino, Alba
Ferrer, Nadia
Marinova, Dessislava
Anel, Alberto
Martin, Carlos
Pardo, Julian
author_sort Aporta, Adriana
collection PubMed
description It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG) were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection.
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spelling pubmed-34469662012-10-01 Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death Aporta, Adriana Arbues, Ainhoa Aguilo, Juan I. Monzon, Marta Badiola, Juan J. de Martino, Alba Ferrer, Nadia Marinova, Dessislava Anel, Alberto Martin, Carlos Pardo, Julian PLoS One Research Article It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG) were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection. Public Library of Science 2012-09-19 /pmc/articles/PMC3446966/ /pubmed/23028853 http://dx.doi.org/10.1371/journal.pone.0045213 Text en © 2012 Aporta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Aporta, Adriana
Arbues, Ainhoa
Aguilo, Juan I.
Monzon, Marta
Badiola, Juan J.
de Martino, Alba
Ferrer, Nadia
Marinova, Dessislava
Anel, Alberto
Martin, Carlos
Pardo, Julian
Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death
title Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death
title_full Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death
title_fullStr Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death
title_full_unstemmed Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death
title_short Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death
title_sort attenuated mycobacterium tuberculosis so2 vaccine candidate is unable to induce cell death
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446966/
https://www.ncbi.nlm.nih.gov/pubmed/23028853
http://dx.doi.org/10.1371/journal.pone.0045213
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