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Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal

Uwe Koedel1, Tobias Frankenberg, Susanne Kirschnek

  • 1Department of Neurology, Clinic of the University of Munich, Munich, Germany.

Plos Pathogens
|May 30, 2009
PubMed

Insights

Neutrophil apoptosis is crucial for resolving inflammation during bacterial meningitis. Inhibiting neutrophil apoptosis worsens disease, while promoting it accelerates recovery, suggesting therapeutic potential.

Area of Science:

  • Immunology
  • Neuroscience
  • Microbiology

Background:

  • Neutrophils combat bacterial infections but can cause tissue damage.
  • Neuronal damage in pneumococcal meningitis often persists despite antibiotic treatment.
  • Excessive neutrophil activity may contribute to this persistent damage.

Purpose of the Study:

  • To investigate the role of neutrophil apoptosis in resolving inflammation during pneumococcal meningitis.
  • To evaluate the therapeutic potential of modulating neutrophil apoptosis.

Main Methods:

  • Used a mouse model of pneumococcal meningitis.
  • Genetically modified hematopoietic cells to express Bcl-2, inhibiting apoptosis.
  • Administered roscovitine, a kinase inhibitor, to induce apoptosis.
  • Assessed neutrophil infiltration, inflammatory markers (IL-1beta, G-CSF, TGF-beta), and disease severity.

Main Results:

  • Bcl-2 expression blocked neutrophil apoptosis and inflammation resolution.
  • Persistent neutrophils correlated with increased IL-1beta, G-CSF, and reduced TGF-beta.
  • Bcl-2 transgenic mice showed exacerbated disease, including edema, vasculitis, and hemorrhage.
  • Roscovitine induced neutrophil apoptosis in vitro and in vivo, improving inflammation resolution and recovery in infected mice.

Conclusions:

  • Neutrophil apoptosis is essential for resolving inflammation and preventing tissue damage in bacterial meningitis.
  • Targeting the neutrophil apoptotic pathway offers a potential therapeutic strategy to modulate inflammatory activity and disease severity.

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