Reference : Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Immunology & infectious disease
Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells.
Bruckner, Shane [> > > >]
Rahmouni, Souad mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Tautz, Lutz [> > > >]
Denault, Jean-Bernard [> > > >]
Alonso, Andres [> > > >]
Becattini, Barbara [> > > >]
Salvesen, Guy S [> > > >]
Mustelin, Tomas [> > > >]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBi)
[en] Annexin A5/chemistry/pharmacology ; Apoptosis ; Bacterial Outer Membrane Proteins/metabolism/physiology ; Caspases/metabolism ; Cell Death ; Cell Separation ; DNA Fragmentation ; Enzyme Activation ; Flow Cytometry ; Hela Cells ; Humans ; Jurkat Cells ; Mitochondria/metabolism/pathology ; Mutagenesis, Site-Directed ; Nucleosomes/metabolism ; Phosphorylation ; Protein Tyrosine Phosphatases/metabolism/physiology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction ; T-Lymphocytes/cytology/pathology ; Transfection ; Yersinia pestis/enzymology ; bcl-X Protein
[en] To evade the immune system, the etiologic agent of plague, Yersinia pestis, injects an exceptionally active tyrosine phosphatase called YopH into host cells using a type III secretion system. We recently reported that YopH acutely inhibits T cell antigen receptor signaling by dephosphorylating the Lck tyrosine kinase. Here, we show that prolonged presence of YopH in primary T cells or Jurkat T leukemia cells causes apoptosis, detected by annexin V binding, mitochondrial breakdown, caspase activation, and internucleosomal fragmentation. YopH also causes cell death when expressed in HeLa cells, and this cell death was inhibited by YopH-specific small molecule inhibitors. Cell death induced by YopH was also prevented by caspase inhibition or co-expression of Bcl-xL. We conclude that YopH not only paralyzes T cells acutely, but also ensures that the cells will not recover to induce a protective immune response but instead undergo mitochondrially regulated programmed cell death.
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