Research output: Contribution to journal › Article › Academic › peer-review
Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia. / van den Boogaard, Florry E.; van Gisbergen, Klaas P. J. M.; Vernooy, Juanita H. et al.
In: American journal of physiology. Lung cellular and molecular physiology, Vol. 311, No. 2, 2016, p. L507-L516.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia
AU - van den Boogaard, Florry E.
AU - van Gisbergen, Klaas P. J. M.
AU - Vernooy, Juanita H.
AU - Medema, Jan P.
AU - Roelofs, Joris J. T. H.
AU - van Zoelen, Marieke A. D.
AU - Endeman, Henrik
AU - Biesma, Douwe H.
AU - Boon, Louis
AU - van't Veer, Cornelis
AU - de Vos, Alex F.
AU - van der Poll, Tom
PY - 2016
Y1 - 2016
N2 - 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
AB - 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
U2 - 10.1152/ajplung.00116.2016
DO - 10.1152/ajplung.00116.2016
M3 - Article
C2 - 27343190
VL - 311
SP - L507-L516
JO - American journal of physiology. Lung cellular and molecular physiology
JF - American journal of physiology. Lung cellular and molecular physiology
SN - 1040-0605
IS - 2
ER -
ID: 2936271