Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells.
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.
Bruckner
Shane
S
Program of Inflammation, Infectious and Inflammatory Disease Center, Cancer Center, The Burnham Institute, La Jolla, California 92037, USA.
Rhamouni
Souad
S
Tautz
Lutz
L
Denault
Jean-Bernard
JB
Alonso
Andres
A
Becattini
Barbara
B
Salvesen
Guy S
GS
Mustelin
Tomas
T
D017304:Annexin A5 / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002469:Cell Separation; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D016297:Mutagenesis, Site-Directed; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000473:pathology*; D014162:Transfection; D015010:Yersinia pestis / Q000201:enzymology*; D051020:bcl-X Protein
D017304:Annexin A5; C494811:BCL2L1 protein, human; D001425:Bacterial Outer Membrane Proteins; D009707:Nucleosomes; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D020169:Caspases