Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia

Florry E. van den Boogaard*, Klaas P. J. M. van Gisbergen, Juanita H. Vernooy, Jan P. Medema, Joris J. T. H. Roelofs, Marieke A. D. van Zoelen, Henrik Endeman, Douwe H. Biesma, Louis Boon, Cornelis van't Veer, Alex F. de Vos, Tom van der Poll

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia (CAP). Granzyme A (GzmA) is a serine protease produced by a variety of cell types involved in the immune response. We sought to determine the role of GzmA on the host response during pneumococcal pneumonia. GzmA was measured in bronchoalveolar lavage fluid (BALF) harvested from CAP patients from the infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels were increased in BALF obtained from the infected lung. Human lungs showed constitutive GzmA expression by both parenchymal and nonparenchymal cells. In an experimental setting, pneumonia was induced in wild-type (WT) and GzmA-deficient (GzmA(-/-)) mice by intranasal inoculation of S. pneumoniae. In separate experiments, WT and GzmA-/- mice were treated with natural killer (NK) cell depleting antibodies. Upon infection with S. pneumoniae, GzmA(-/-) mice showed a better survival and lower bacterial counts in BALF and distant body sites compared with WT mice. Although NK cells showed strong GzmA expression, NK cell depletion did not influence bacterial loads in either WT or GzmA(-/-) mice. These results implicate that GzmA plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on NK cells.
Original languageEnglish
Pages (from-to)L507-L516
JournalAmerican Journal of Physiology-Lung Cellular and Molecular Physiology
Issue number2
Publication statusPublished - 1 Aug 2016


  • inflammation
  • pneumonia
  • Streptococcus pneumoniae
  • granzyme A


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