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

Streptococcus pneumoniae is the major cause of bacterial meningitis and it damages the hippocampus by inducing neuronal apoptosis. The blocking of cas pases provides only partial protection in experimental meningitis, which su ggests that there is an additional apoptotic pathway. A trigger of this pat hway is the bacterium itself, as exposure of microglia or neurons to live p neumococci induces rapid apoptosis. In this study, apoptosis was not associ ated with the activation of caspases-1-10 and was not inhibited by z-VAD-fm k, a broad-spectrum caspase inhibitor. Rather, apoptosis was attributed to damage to mitochondria, which was followed by the release of apoptosis-indu cing factor (AIF) from the mitochondria, large-scale DNA fragmentation, and hypodiploidy. Furthermore, intracytoplasmatic microinjection of AIF-specif ic antiserum markedly impaired pneumococcus-induced apoptosis. These findin gs indicate that AIF may play a central role in brain cell apoptosis and ba cterial pathogenesis.