Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 11, Pages 2981-2992Publisher
WILEY
DOI: 10.1002/eji.200838761
Keywords
Caspase-1; IRF; mTOR; TLR
Categories
Funding
- Deutsche Forschungsgemeinschaft [TR22/45]
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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-1 beta. Mechanistically, mTOR suppresses caspase-1 activation, thus inhibits release of bioactive IL-1 beta. We have identified mTOR as indispensable component of PRR signal pathways, which orchestrates the defense program of innate immune cells.
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