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

Braun JS, Novak R, Murray PJ, Eischen CM, Susin SA, Kroemer G, Halle A, Weber JR, Tuomanen EI, Cleveland JL
J Infect Dis. 2001 184 (10): 1300-9

PMID: 11679919 · DOI:10.1086/324013

Streptococcus pneumoniae is the major cause of bacterial meningitis and it damages the hippocampus by inducing neuronal apoptosis. The blocking of caspases provides only partial protection in experimental meningitis, which suggests that there is an additional apoptotic pathway. A trigger of this pathway is the bacterium itself, as exposure of microglia or neurons to live pneumococci induces rapid apoptosis. In this study, apoptosis was not associated with the activation of caspases-1-10 and was not inhibited by z-VAD-fmk, a broad-spectrum caspase inhibitor. Rather, apoptosis was attributed to damage to mitochondria, which was followed by the release of apoptosis-inducing factor (AIF) from the mitochondria, large-scale DNA fragmentation, and hypodiploidy. Furthermore, intracytoplasmatic microinjection of AIF-specific antiserum markedly impaired pneumococcus-induced apoptosis. These findings indicate that AIF may play a central role in brain cell apoptosis and bacterial pathogenesis.

MeSH Terms (19)

Animals Apoptosis Apoptosis Inducing Factor Brain Cell Line Cell Nucleus Diploidy DNA DNA Fragmentation Flavoproteins Humans Membrane Proteins Meningitis, Bacterial Mice Microglia Mitochondria Neurons Pneumococcal Infections Streptococcus pneumoniae

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