Granzyme A Is Expressed in Mouse Lungs during Mycobacterium tuberculosis Infection but Does Not Contribute to Protection In Vivo

Uranga, S (Universidad de Zaragoza) ; Marinova, D (Universidad de Zaragoza) ; Martin, C (Universidad de Zaragoza) ; Pardo, J (Universidad de Zaragoza) ; Aguilo, N (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1371/journal.pone.0153028

Año: 2016

Publicado en: PloS one 11, 4 (2016), [8 pp]
ISSN: 1932-6203

Factor impacto JCR: 2.806 (2016)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 15 / 63 = 0.238 (2016) - Q1 - T1

Factor impacto SCIMAGO: 1.236 - Agricultural and Biological Sciences (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Área Inmunología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Med.Pr.,Sal.Públ.)