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

• Published in: The Journal of infectious diseases Vol. 184; no. 10; pp. 1300 - 1309
• Main Authors: Braun, Johann S., Novak, Rodger, Murray, Peter J., Eischen, Christine M., Susin, Santos A., Kroemer, Guido, Halle, Annett, Weber, Joerg R., Tuomanen, Elaine I., Cleveland, John L.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.11.2001; University of Chicago Press
• Subjects: Animals; Apoptosis; Apoptosis Inducing Factor; Bacteriology; Biological and medical sciences; Brain; Brain damage; Cell Line; Cell lines; Cell nucleus; Cell Nucleus - chemistry; Cell Nucleus - pathology; Cytochromes; Diploidy; DNA - metabolism; DNA damage; DNA Fragmentation; Flavoproteins - metabolism; Flavoproteins - physiology; Fundamental and applied biological sciences. Psychology; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Major Articles; Medical sciences; Membrane Proteins - metabolism; Membrane Proteins - physiology; Meningitis, Bacterial - physiopathology; Mice; Microbiology; Microglia; Microglia - microbiology; Microglia - pathology; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Neurons; Neurons - microbiology; Neurons - pathology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Pneumococcal Infections - physiopathology; Streptococcus pneumoniae; Streptococcus pneumoniae - physiology; Nervous system diseases; Enzyme; Pathogenesis; Central nervous system; Caspase; Streptococcus pneumoniae; Infection; Peptidases; Streptococcaceae; Mitochondria; Specificity; Neuron; Cell death; Streptococcal infection; Central nervous system disease; Bacteriosis; Bacteria; Hydrolases; Micrococcales; Meningitis; Release; Apoptosis; Brain (vertebrata)
• ISSN: 0022-1899; 1537-6613
• 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