Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells
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-1beta. Mechanistically, mTOR suppresses caspase-1 activation, thus inhibits release of bioactive IL-1beta. We have identified mTOR as indispensable component of PRR signal pathways, which orchestrates the defense program of innate immune cells.
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mTOR suppresses caspase-1 activation and orchestrates the defence programme of innate immune cells.
“Third, mTOR suppresses caspase-1 activation and orchestrates the defence programme of innate immune cells [149].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [149]
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Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling
Schoenemeyer, A., Barnes, B. J., Mancl, M. E., Latz, E., Goutagny, N., Pitha, P. M., Fitzgerald, K. A., & Golenbock, D. T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412584200 · Cited by 411 · see citing works
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Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells
Weichhart, T., Haidinger, M., Katholnig, K., Kopecky, C., Poglitsch, M., Lassnig, C., Rosner, M., Zlabinger, G. J., Hengstschläger, M., Müller, M., et al. (2011) · Blood · doi:10.1182/blood-2010-09-310888 · Cited by 141 · see citing works
Boer, K., Crino, P. B., Gorter, J. A., Nellist, M., Jansen, F. E., Spliet, W. G. M., Van Rijen, P. C., Wittink, F. R. A., Breit, T. M., Troost, D., et al. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2009.00341.x · Cited by 148 · see citing works
Regulation of the autophagic machinery in human neutrophils
Mitroulis, I., Kourtzelis, I., Kambas, K., Rafail, S., Chrysanthopoulou, A., Speletas, M., & Ritis, K. (2010) · European Journal of Immunology · doi:10.1002/eji.200940025 · Cited by 132 · see citing works
Dello Russo, C., Lisi, L., Feinstein, D. L., & Navarra, P. (2013) · Glia · doi:10.1002/glia.22433 · Cited by 96 · see citing works
PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease
Morel, M., Couturier, J., Lafay‐Chebassier, C., Paccalin, M., & Page, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00849.x · Cited by 47 · see citing works
- Authors
- Schmitz, F., Heit, A., Dreher, S., Eisenächer, K., Mages, J., Haas, T., Krug, A., Janssen, K., Kirschning, C. J., & Wagner, H.
- Affiliations
- Technical University of Munich (DE)
- TUM Klinikum (DE)
- Corresponding author
- Wagner, Hermann
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2008-11
- Volume
- 38
- Issue
- 11
- Pages
- 2981-2992
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2082827804
- Cited by
- 212
- References
- 2
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 16 · 2021: 14 · 2020: 14 · 2019: 8 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 15 · 2014: 19 · 2013: 19 · 2012: 14
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- mTOR, innate immunity, Toll-like receptor signaling, MyD88, phosphoinositide 3-kinase/Akt pathway, IRF5, IRF7, type I interferon, inflammatory cytokines, endotoxic shock, IL-1β, caspase-1 activation, pattern recognition receptors
- MeSH terms
- Animals, Cells, Cultured, Female, Humans, Immunity, Innate, Lipopolysaccharides, Mice, Inbred C57BL, Protein Kinases, Transcription, Genetic, Signal Transduction, Cytokines, Caspase 1, Interferon Regulatory Factor-7, Toll-Like Receptors, Mice, Interleukin-1beta, TOR Serine-Threonine Kinases
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