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
Summary
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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