Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways
Daniela Bermpohl, … , Nicolas W.J. Schröder, Joerg R. Weber
Daniela Bermpohl, … , Nicolas W.J. Schröder, Joerg R. Weber
Published June 1, 2005
Citation Information: J Clin Invest. 2005;115(6):1607-1615. https://doi.org/10.1172/JCI23223.
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Research Article Infectious disease

Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways

Abstract

Major barriers separating the blood from tissue compartments in the body are composed of endothelial cells. Interaction of bacteria with such barriers defines the course of invasive infections, and meningitis has served as a model system to study endothelial cell injury. Here we report the impressive ability of Streptococcus pneumoniae, clinically one of the most important pathogens, to induce 2 morphologically distinct forms of programmed cell death (PCD) in brain-derived endothelial cells. Pneumococci and the major cytotoxins H202 and pneumolysin induce apoptosis-like PCD independent of TLR2 and TLR4. On the other hand, pneumococcal cell wall, a major proinflammatory component, causes caspase-driven classical apoptosis that is mediated through TLR2. These findings broaden the scope of bacterial-induced PCD, link these effects to innate immune TLRs, and provide insight into the acute and persistent phases of damage during meningitis.

Authors

Daniela Bermpohl, Annett Halle, Dorette Freyer, Emilie Dagand, Johann S. Braun, Ingo Bechmann, Nicolas W.J. Schröder, Joerg R. Weber

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Role of caspases in pneumococcal PCD. Living pneumococci failed to activ...
Role of caspases in pneumococcal PCD. Living pneumococci failed to activate caspase-3 and caspase-9. Staurosporine (ST) activated both caspases (A and C). PCW induced caspase-3 and caspase-8 activity (B and D; gray bars indicate PCW challenge; white bars indicate controls). AMC, 7-amino-4-methyl coumarin). Prot, protein. (E and F) According to Western blot analysis, in contrast to living pneumococci, staurosporine and PCW caused the cleavage of fodrin after exposure. (G) z-VAD-fmk (z-VAD), a broad-spectrum caspase inhibitor, and z-DEVD-cho (z-DEVD), a specific caspase-3 inhibitor, did not prevent PCD induced by living pneumococci (D39). Black bar: S. pneumoniae only. (H) Both inhibitors blocked PCD caused by PCW. Gray bar: PCW only. Data are presented as mean ± SD. *P < 0.05 (ANOVA and Student-Newman-Keuls test).