| First Author | Schmitz F | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 11 | Pages | 2981-92 |
| PubMed ID | 18924132 | Mgi Jnum | J:143270 |
| Mgi Id | MGI:3826306 | Doi | 10.1002/eji.200838761 |
| Citation | Schmitz F, et al. (2008) Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells. Eur J Immunol 38(11):2981-92 |
| abstractText | 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. |
