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Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia

Florry E van den Boogaard1, Klaas P J M van Gisbergen2, Juanita H Vernooy3

  • 1Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; f.e.vandenboogaard@amc.nl.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|June 26, 2016
PubMed

Insights

Granzyme A (GzmA) worsens outcomes in bacterial pneumonia. Studies show GzmA deficiency improves survival and reduces bacterial load in Streptococcus pneumoniae pneumonia, independent of natural killer cells.

Area of Science:

  • Immunology
  • Pulmonology
  • Microbiology

Background:

  • Streptococcus pneumoniae is a leading cause of community-acquired pneumonia (CAP).
  • Granzyme A (GzmA), a serine protease, is involved in immune responses.
  • The specific role of GzmA in pneumococcal pneumonia pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the role of Granzyme A (GzmA) in the host immune response during pneumococcal pneumonia.
  • To determine if GzmA influences disease severity and bacterial clearance in a mouse model of pneumonia.

Main Methods:

  • GzmA levels were quantified in bronchoalveolar lavage fluid (BALF) and lung tissue from CAP patients.
  • Pneumonia was induced in wild-type (WT) and GzmA-deficient (GzmA(-/-)) mice via intranasal inoculation of Streptococcus pneumoniae.
  • Natural killer (NK) cells were depleted in separate experiments using depleting antibodies.

Main Results:

  • Elevated GzmA levels were observed in BALF from infected lungs of CAP patients.
  • GzmA(-/-) mice exhibited improved survival rates and reduced bacterial burdens in BALF and distant sites compared to WT mice.
  • NK cell depletion did not significantly alter bacterial loads in either WT or GzmA(-/-) mice, suggesting a non-NK cell-dependent mechanism.

Conclusions:

  • Granzyme A plays a detrimental role in host defense during Streptococcus pneumoniae pneumonia.
  • The unfavorable effect of GzmA is mediated through a mechanism independent of natural killer cells.
Keywords:
Streptococcus pneumoniaegranzyme Ainflammationpneumonia

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