Legionella pneumophila induces apoptosis via the mitochondrial death pathway.
Legionella pneumophila has been shown to induce apoptosis within macrophages, monocytic cell lines and alveolar epithelial cells. The mechanisms and significance of L. pneumophila-associated apoptosis are not well understood. It has been speculated that L. pneumophila may induce apoptosis through ligation of death receptors by bacterial surface components or by secreted bacterial factors. Translocation of apoptotic factor(s) through the Dot/Icm secretion machinery followed by direct activation of caspases within the cytosol is discussed as another possible mechanism of apoptosis induction by L. pneumophila. Here, it is shown that L. pneumophila induced the mitochondrial release of cytochrome c in CD95 (Fas/Apo-1)-negative monocytic Mono Mac 6 cells, indicating that Legionella-induced apoptosis is mediated via the mitochondrial signalling pathway. In addition, blocking of the death receptor pathway at distinct stages using CD95-, FADD- or caspase-8-deficient Jurkat cells did not affect induction of apoptosis by L. pneumophila. Conversely, inhibition of the mitochondrial death pathway by overexpression of the anti-apoptotic protein Bcl-2 potently inhibited the processing of caspases and the induction of apoptosis. Therefore, these findings support a model in which the induction of apoptosis by L. pneumophila is mediated by activation of the intrinsic mitochondrial death pathway in the absence of external death receptor signalling.
Neumeister
Birgid
B
Department of Transfusion Medicine, University Hospital of Tübingen, Otfried-Müller-Strasse 4/1, D-72076 Tübingen, Germany1.
Faigle
Marion
M
Department of Transfusion Medicine, University Hospital of Tübingen, Otfried-Müller-Strasse 4/1, D-72076 Tübingen, Germany1.
Lauber
Kirsten
K
Department of Internal Medicine I, University Hospital of Tübingen, Otfried-Müller-Strasse 10, D-72076 Tübingen, Germany2.
Northoff
Hinnak
H
Department of Transfusion Medicine, University Hospital of Tübingen, Otfried-Müller-Strasse 4/1, D-72076 Tübingen, Germany1.
Wesselborg
Sebastian
S
Department of Internal Medicine I, University Hospital of Tübingen, Otfried-Müller-Strasse 10, D-72076 Tübingen, Germany2.
D017209:Apoptosis; D002478:Cells, Cultured; D006801:Humans; D019169:Jurkat Cells; D016952:Legionella pneumophila / Q000502:physiology*; D007877:Legionnaires' Disease / Q000473:pathology*; D008264:Macrophages / Q000166:cytology* / Q000382:microbiology; D008928:Mitochondria / Q000502:physiology*; D009000:Monocytes / Q000166:cytology* / Q000382:microbiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053219:Receptors, Tumor Necrosis Factor, Member 25; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; D019014:fas Receptor