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

PLoS One. 2016 Apr 7;11(4):e0153028. doi: 10.1371/journal.pone.0153028. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Enzymologic*
  • Granzymes / genetics
  • Granzymes / metabolism*
  • Lung / enzymology*
  • Lung / pathology
  • Mice
  • Mice, Knockout
  • Mycobacterium tuberculosis*
  • Tuberculosis Vaccines / pharmacology
  • Tuberculosis, Pulmonary / enzymology*
  • Tuberculosis, Pulmonary / genetics
  • Tuberculosis, Pulmonary / pathology
  • Tuberculosis, Pulmonary / prevention & control

Substances

  • Tuberculosis Vaccines
  • Granzymes
  • granzyme A, mouse

Grant support

This work was supported by the Spanish Ministry of Economy and Competitiveness (grant numbers SAF2014-54763-C2-1-R, BIO2014-5258P) and the European Commission (grant number TBVAC2020 643381). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.