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

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

doi:10.1172/JCI23223

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

J Clin Invest. 2005 Jun;115(6):1607-15. doi: 10.1172/JCI23223. Epub 2005 May 2.

Authors

Daniela Bermpohl¹, Annett Halle, Dorette Freyer, Emilie Dagand, Johann S Braun, Ingo Bechmann, Nicolas W J Schröder, Joerg R Weber

Affiliation

¹ Department of Neurology, Center of Anatomy, Charité--Universitätsmedizin Berlin, Berlin, Germany.

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 H2O2 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis* / drug effects
Bacterial Proteins / pharmacology
Caspases / metabolism
Cell Wall / metabolism
Cells, Cultured
Cerebellum / cytology
Cerebellum / pathology
Cerebellum / physiopathology*
Endothelial Cells / metabolism*
Endothelial Cells / microbiology
Endothelial Cells / pathology
Hydrogen Peroxide / pharmacology
Membrane Glycoproteins / deficiency
Membrane Glycoproteins / metabolism
Meningitis, Pneumococcal / microbiology
Meningitis, Pneumococcal / pathology
Meningitis, Pneumococcal / physiopathology*
Mice
Mice, Knockout
Rats
Rats, Wistar
Receptors, Cell Surface / deficiency
Receptors, Cell Surface / metabolism
Streptococcus pneumoniae*
Streptolysins / pharmacology
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors

Substances

Bacterial Proteins
Membrane Glycoproteins
Receptors, Cell Surface
Streptolysins
Tlr2 protein, rat
Tlr4 protein, rat
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
plY protein, Streptococcus pneumoniae
Hydrogen Peroxide
Caspases