Eur J Immunol 2008,
PMID: 18924132
Schmitz, Frank; Heit, Antje; Dreher, Stefan; Eisenächer, Katharina; Mages, Jörg; Haas, Tobias; Krug, Anne; Janssen, Klaus-Peter; Kirschning, Carsten J; Wagner, Hermann
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.
Document information provided by NCBI PubMed
Text Mining Data
mTOR → TLR: "
Here we demonstrate that
TLR activate
mTOR via phosphoinositide 3-kinase/Akt
"
Manually curated Databases
No curated data.