Article (Scientific journals)
Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells.
Bruckner, Shane; Rahmouni, Souad; Tautz, Lutz et al.
2005In Journal of Biological Chemistry, 280 (11), p. 10388-94
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Keywords :
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
Abstract :
[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.
Disciplines :
Immunology & infectious disease
Biochemistry, biophysics & molecular biology
Author, co-author :
Bruckner, Shane
Rahmouni, Souad  ;  Université de Liège - ULiège > 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
Language :
English
Title :
Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells.
Publication date :
2005
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
280
Issue :
11
Pages :
10388-94
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 January 2009

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