Highlights

Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells

  1. Frank Schmitz1,
  2. Antje Heit1,
  3. Stefan Dreher1,
  4. Katharina Eisenächer2,
  5. Jörg Mages1,
  6. Tobias Haas1,
  7. Anne Krug2,
  8. Klaus-Peter Janssen3,
  9. Carsten J. Kirschning1,
  10. Hermann Wagner1,*

Article first published online: 15 OCT 2008

DOI: 10.1002/eji.200838761

Issue

European Journal of Immunology

European Journal of Immunology

Volume 38, Issue 11, pages 2981–2992, November 2008

Additional Information

How to Cite

Schmitz, F., Heit, A., Dreher, S., Eisenächer, K., Mages, J., Haas, T., Krug, A., Janssen, K.-P., Kirschning, C. J. and Wagner, H. (2008), Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells. Eur. J. Immunol., 38: 2981–2992. doi: 10.1002/eji.200838761

Author Information

  1. 1

    Institut fuer Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universitaet Muenchen, Muenchen, Germany

  2. 2

    II. Med. Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany

  3. 3

    Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Muenchen, Germany

*Institut fuer Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universitaet Muenchen, Trogerstr. 30, 81675 Muenchen, Germany Fax: +49-89-4140-4139

Publication History

  1. Issue published online: 7 NOV 2008
  2. Article first published online: 15 OCT 2008
  3. Manuscript Accepted: 21 AUG 2008
  4. Manuscript Revised: 20 AUG 2008
  5. Manuscript Received: 28 JUL 2008

Funded by

  • Deutsche Forschungsgemeinschaft. Grant Number: TR22/45

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Keywords:

  • Caspase-1;
  • IRF;
  • mTOR;
  • TLR

Abstract

The mammalian target of rapamycin (mTOR) can be viewed as cellular master complex scoring cellular vitality and stress. Whether mTOR controls also innate immune-defenses is currently unknown. Here we demonstrate that TLR activate mTOR via phosphoinositide 3-kinase/Akt. mTOR physically associates with the MyD88 scaffold protein to allow activation of interferon regulatory factor-5 and interferon regulatory factor-7, known as master transcription factors for pro-inflammatory cytokine- and type I IFN-genes. Unexpectedly, inactivation of mTOR did not prevent but increased lethality of endotoxin-mediated shock, which correlated with increased levels of IL-1β. Mechanistically, mTOR suppresses caspase-1 activation, thus inhibits release of bioactive IL-1β. We have identified mTOR as indispensable component of PRR signal pathways, which orchestrates the defense program of innate immune cells.

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