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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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Published on: December 27, 2016

Apoptosis-inducing factor mediates microglial and neuronal apoptosis caused by pneumococcus

J S Braun1, R Novak, P J Murray

  • 1Department of Infectious Diseases, St. Jude Children's Research Hospital, University of Tennessee, Memphis, TN 38105, USA.

The Journal of Infectious Diseases
|October 27, 2001
PubMed

Insights

Streptococcus pneumoniae induces brain cell death via a novel pathway. Apoptosis-Inducing Factor (AIF) release from mitochondria, not caspases, drives this damage during bacterial meningitis.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Streptococcus pneumoniae is a primary cause of bacterial meningitis.
  • Pneumococcal meningitis leads to hippocampal damage via neuronal apoptosis.
  • Caspase inhibition offers only partial protection, indicating alternative apoptotic pathways.

Purpose of the Study:

  • To investigate the mechanism of pneumococcus-induced apoptosis in brain cells.
  • To identify the specific pathway involved in bacterial meningitis-related neuronal damage.

Main Methods:

  • Exposure of microglia and neurons to live Streptococcus pneumoniae.
  • Assessment of apoptosis in the absence of caspase activation.
  • Mitochondrial damage and apoptosis-inducing factor (AIF) release analysis.
  • Inhibition of apoptosis using AIF-specific antiserum.

Main Results:

  • Pneumococcus-induced apoptosis was not mediated by caspases-1-10.
  • Apoptosis correlated with mitochondrial damage and AIF release.
  • Large-scale DNA fragmentation and hypodiploidy were observed.
  • AIF antiserum significantly reduced pneumococcus-induced apoptosis.

Conclusions:

  • Apoptosis-Inducing Factor (AIF) plays a critical role in Streptococcus pneumoniae-induced brain cell apoptosis.
  • AIF-mediated cell death represents a key pathway in bacterial meningitis pathogenesis.
  • Targeting AIF may offer new therapeutic strategies for pneumococcal meningitis.

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