Apoptosis-Inducing Factor Mediates Microglial and Neuronal Apoptosis Caused by Pneumococcus

J. S. Braun, R. Novak, P. J. Murray, C. M. Eischen, S. A. Susin, G. Kroemer, A. Halle, J. R. Weber, E. I. Tuomanen, J. L. Cleveland

Research output: Contribution to journalArticlepeer-review

113 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1300-1309
Number of pages10
JournalJournal of Infectious Diseases
Volume184
Issue number10
DOIs
Publication statusPublished - Nov 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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