Publication

Staphylococcus aureus alpha-toxin induces apoptosis in peripheral blood mononuclear cells: role of endogenous tumour necrosis factor-alpha and the mitochondrial death pathway

Haslinger, B., Strangfeld, K., Peters, G., Schulze-Osthoff, K. & Sinha, B., Oct-2003, In : Cellular Microbiology. 5, 10, p. 729-741 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Bettina Haslinger
  • Katrin Strangfeld
  • Georg Peters
  • Klaus Schulze-Osthoff
  • Bhanu Sinha

Staphylococcus aureus infections can result in septic and toxic shock with depletion of immune cells and massive cytokine production. Recently, we showed that, in S. aureus-infected Jurkat T cells, alpha-toxin is the major mediator of caspase activation and apoptosis. Here, we investigated the mechanisms of cell death induced by alpha-toxin in peripheral blood mononuclear cells (MNC). We show that alpha-toxin is required and sufficient for S. aureus-induced cell death not only in transformed Jurkat T cells but also in MNC. Low alpha-toxin doses (3-30 ng ml-1) dose- and time-dependently induced apoptosis in both cell types, which was completely blocked by the caspase inhibitor zVAD-fmk. In Jurkat T cells and MNC, alpha-toxin induced the breakdown of the mitochondrial membrane potential and the intrinsic activation of caspase-3, -8 and -9. Interestingly, unlike in Jurkat T cells, apoptosis in MNC was additionally mediated by a caspase-9-independent component. MNC, but not Jurkat T cells, produced tumour necrosis factor (TNF)-alpha upon alpha-toxin stimulation. Blocking endogenous TNF-alpha with a TNF-alpha receptor antagonist partially decreased apoptosis in MNC. Our data therefore suggest that, whereas in Jurkat T cells apoptosis is solely mediated by the mitochondrial pathway, in MNC endogenous TNF-alpha and a death receptor-dependent pathway are also involved, which may contribute to depletion of immune cells during S. aureus infection.

Original languageEnglish
Pages (from-to)729-741
Number of pages13
JournalCellular Microbiology
Volume5
Issue number10
Publication statusPublished - Oct-2003

    Keywords

  • Amino Acid Chloromethyl Ketones, Apoptosis, Bacterial Toxins, Caspase 3, Caspase 8, Caspase 9, Caspase Inhibitors, Caspases, Enzyme Activation, Hemolysin Proteins, Humans, Jurkat Cells, Leukocytes, Mononuclear, Membrane Potentials, Mitochondria, Staphylococcus aureus, Tumor Necrosis Factor-alpha

ID: 13979709