title: Granzyme A Is Expressed in Mouse Lungs during Mycobacterium tuberculosis Infection but Does Not Contribute to Protection In Vivo.
abstract: Granzyme A, a serine protease expressed in the granules of cytotoxic T and Natural Killer cells, is involved in the generation of pro-inflammatory cytokines by macrophages. Granzyme A has been described to induce in macrophages in vitro the activation of pro-inflammatory pathways that impair intracellular mycobacterial replication. In the present study, we explored the physiological relevance of Granzyme A in the control of pulmonary Mycobacterium tuberculosis infection in vivo. Our results show that, even though Granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of M. tuberculosis infection. In addition our findings indicate that absence of Granzyme A does not affect the protection conferred by the live-attenuated M. tuberculosis vaccine MTBVAC. Altogether, our findings are in apparent contradiction with previously published in vitro results and suggest that Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis.
authors.affiliation: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, C/ Domingo Miral s/n, 50009, Zaragoza, Spain.|CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Uranga
authors.affiliation: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, C/ Domingo Miral s/n, 50009, Zaragoza, Spain.|CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Dessislava
authors.initials: D
authors.lastname: Marinova
authors.affiliation: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, C/ Domingo Miral s/n, 50009, Zaragoza, Spain.|CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.|Servicio de Microbiología, Hospital Universitario Miguel Servet, ISS Aragón, Paseo Isabel la Católica 1-3, 50009, Zaragoza, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martin
authors.affiliation: Immune Effector Cells Group (ICE), 3 Aragón Health Research Institute (IIS Aragón), Edificio CIBA, Biomedical Research Centre of Aragón (CIBA), Zaragoza, Spain.|Nanoscience Institute of Aragon (INA), University of Zaragoza, Zaragoza, Spain.|Fundación Aragón I+D (ARAID), Gobierno de Aragón, Zaragoza, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
authors.affiliation: Grupo de Genética de Micobacterias, Dpto. Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, C/ Domingo Miral s/n, 50009, Zaragoza, Spain.|CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Nacho
authors.initials: N
authors.lastname: Aguilo
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D053804:Granzymes / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control
chemical_list: D032581:Tuberculosis Vaccines; D053804:Granzymes; C000597315:granzyme A, mouse