Legionella pneumophila is the causative agent of human Legionnaires' disease. L. pneumophila has been shown to induce apoptosis of T-cells and this may be important pathologically and clinically. The present study has determined the molecular mechanisms underlying L. pneumophila-induced apoptosis, which were unclear. Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T-cells. However, apoptosis was efficiently induced in T-cells only by wild-type L. pneumophila, and not flagellin-deficient or Dot/Icm-deficient Legionella. Induction of apoptosis involved activation of the initiator caspase 9 and effector caspase 3. Infection with L. pneumophila inhibited phosphorylation of Akt (also known as protein kinase B) and the Akt substrate GSK3β (glycogen synthase kinase 3β), and reduced the levels of β-catenin, a transcriptional activator regulated by GSK3β. It also caused the activation of the pro-apoptotic protein Bax and inhibited the expression of the anti-apoptotic protein XIAP (X-linked inhibitor of apoptosis) via inhibition of the Akt pathway. In conclusion, L. pneumophila induces mitochondria-mediated T-cell apoptosis through inhibition of the Akt/GSK3β signalling pathway.
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Research Article|
March 15 2010
Inhibition of Akt/GSK3β signalling pathway by Legionella pneumophila is involved in induction of T-cell apoptosis
Reika Takamatsu;
Reika Takamatsu
*Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Eriko Takeshima;
Eriko Takeshima
*Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
†Division of Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Chie Ishikawa;
Chie Ishikawa
*Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
‡Transdisciplinary Research Organization for Subtropics and Island Studies, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan
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Kei Yamamoto;
Kei Yamamoto
*Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Hiromitsu Teruya;
Hiromitsu Teruya
*Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
†Division of Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Klaus Heuner;
Klaus Heuner
§Project group 26 “Nosocomial Infections of the Elderly”, Robert Koch-Institut, 20 Nordufer, Berlin 13353, Germany
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Futoshi Higa;
Futoshi Higa
†Division of Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Jiro Fujita;
Jiro Fujita
†Division of Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Naoki Mori
Naoki Mori
1
*Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
1To whom correspondence should be addressed (email n-mori@med.u-ryukyu.ac.jp).
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Publisher: Portland Press Ltd
Received:
November 16 2009
Revision Received:
January 21 2010
Accepted:
January 26 2010
Accepted Manuscript online:
January 26 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 427 (1): 57–67.
Article history
Received:
November 16 2009
Revision Received:
January 21 2010
Accepted:
January 26 2010
Accepted Manuscript online:
January 26 2010
Connected Content
A retraction has been published:
Inhibition of Akt/GSK3β signalling pathway by Legionella pneumophila is involved in induction of T-cell apoptosis
Citation
Reika Takamatsu, Eriko Takeshima, Chie Ishikawa, Kei Yamamoto, Hiromitsu Teruya, Klaus Heuner, Futoshi Higa, Jiro Fujita, Naoki Mori; Inhibition of Akt/GSK3β signalling pathway by Legionella pneumophila is involved in induction of T-cell apoptosis. Biochem J 1 April 2010; 427 (1): 57–67. doi: https://doi.org/10.1042/BJ20091768
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