title: Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.
abstract: 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.
authors.affiliation: Grupo Apoptosis, Inmunidad y Cáncer, Dpto. Bioquímica y Biología Molecular y Celular, Fac. Ciencias, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aporta
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arbues
authors.forename: Juan I
authors.initials: JI
authors.lastname: Aguilo
authors.forename: Marta
authors.initials: M
authors.lastname: Monzon
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badiola
authors.forename: Alba
authors.initials: A
authors.lastname: de Martino
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferrer
authors.forename: Dessislava
authors.initials: D
authors.lastname: Marinova
authors.forename: Alberto
authors.initials: A
authors.lastname: Anel
authors.forename: Carlos
authors.initials: C
authors.lastname: Martin
authors.forename: Julian
authors.initials: J
authors.lastname: Pardo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000382:microbiology / Q000473:pathology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D010718:Phosphatidylserines / Q000737:chemistry; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D014611:Vaccination; D014613:Vaccines, Attenuated; D014774:Virulence
chemical_list: D001500:BCG Vaccine; D010718:Phosphatidylserines; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D053148:Caspase 3