{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:21:51Z","timestamp":1777425711053,"version":"3.51.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.01515","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T04:24:23Z","timestamp":1596774263000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["mTORC1 Is Not Principally Involved in the Induction of Human Endotoxin Tolerance"],"prefix":"10.3389","volume":"11","author":[{"given":"Kristin","family":"Ludwig","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf A.","family":"Husain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-019-0025-4","article-title":"Therapeutic targeting of trained immunity","volume":"18","author":"Mulder","year":"2019","journal-title":"Nat Rev Drug Discov."},{"key":"B2","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1128\/CVI.00688-13","article-title":"Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors","volume":"21","author":"Ifrim","year":"2014","journal-title":"Clin Vaccine Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.it.2009.07.009","article-title":"Endotoxin tolerance: new mechanisms, molecules and clinical significance","volume":"30","author":"Biswas","year":"2009","journal-title":"Trends Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1189\/jlb.3MR0316-118RR","article-title":"Molecular mechanisms of innate memory and tolerance to LPS","volume":"101","author":"Seeley","year":"2017","journal-title":"J Leukoc Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e422","DOI":"10.1016\/S1473-3099(19)30567-5","article-title":"Current gaps in sepsis immunology: new opportunities for translational research","volume":"19","author":"Rubio","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41586-018-0253-5","article-title":"Induction of innate immune memory via microRNA targeting of chromatin remodelling factors","volume":"559","author":"Seeley","year":"2018","journal-title":"Nature."},{"key":"B7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1002\/jcb.27547","article-title":"Recent advances in endotoxin tolerance","volume":"120","author":"Liu","year":"2019","journal-title":"J Cell Biochem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.bbrc.2003.10.019","article-title":"Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients","volume":"311","author":"Escoll","year":"2003","journal-title":"Biochem Biophys Res Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.4049\/jimmunol.1600009","article-title":"Epigenetic and transcriptional regulation of IRAK-M expression in macrophages","volume":"198","author":"Lyroni","year":"2017","journal-title":"J Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1182\/blood.2019000320","article-title":"Signaling mechanisms inducing hyporesponsiveness of phagocytes during systemic inflammation","volume":"134","author":"Freise","year":"2019","journal-title":"Blood."},{"key":"B11","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1002\/eji.201847883","article-title":"IL-10 signaling in dendritic cells is required for tolerance induction in a murine model of allergic airway inflammation","volume":"49","author":"Dolch","year":"2019","journal-title":"Eur J Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1250684","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science."},{"key":"B13","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.smim.2016.09.002","article-title":"Immunometabolic circuits in trained immunity","volume":"28","author":"Arts","year":"2016","journal-title":"Semin Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1083\/jcb.17.3.487","article-title":"Metabolic patterns in three types of phagocytizing cells","volume":"17","author":"Oren","year":"1963","journal-title":"J Cell Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"605","DOI":"10.4049\/jimmunol.0901698","article-title":"Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation","volume":"185","author":"Rodriguez-Prados","year":"2010","journal-title":"J Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell."},{"key":"B17","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1-TSC2 complex: a molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/S1097-2765(03)00220-X","article-title":"Insulin activation of Rheb, a mediator of mTOR\/S6K\/4E-BP signaling, is inhibited by TSC1 and 2","volume":"11","author":"Garami","year":"2003","journal-title":"Mol Cell."},{"key":"B19","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1146\/annurev.immunol.14.1.483","article-title":"Immunopharmacology of rapamycin","volume":"14","author":"Abraham","year":"1996","journal-title":"Annu Rev Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/j.1750-3639.1995.tb00591.x","article-title":"Clinical, neuropathological and genetic aspects of the tuberous sclerosis complex","volume":"5","author":"Short","year":"1995","journal-title":"Brain Pathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/ejhg.2011.241","article-title":"Genotype and cognitive phenotype of patients with tuberous sclerosis complex","volume":"20","author":"van Eeghen","year":"2012","journal-title":"Eur J Hum Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3650","DOI":"10.15252\/embj.201796700","article-title":"Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients","volume":"36","author":"Woodford","year":"2017","journal-title":"EMBO J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2818","DOI":"10.3389\/fimmu.2018.02818","article-title":"Candida albicans beta-glucan differentiates human monocytes into a specific subset of macrophages","volume":"9","author":"Leonhardt","year":"2018","journal-title":"Front Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4129","DOI":"10.4049\/jimmunol.1202611","article-title":"Candida albicans primes TLR cytokine responses through a dectin-1\/Raf-1-mediated pathway","volume":"190","author":"Ifrim","year":"2013","journal-title":"J Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e1006641","DOI":"10.1371\/journal.pgen.1006641","article-title":"Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease","volume":"13","author":"Baillie","year":"2017","journal-title":"PLoS Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2834","DOI":"10.1038\/ncomms3834","article-title":"The TSC-mTOR pathway regulates macrophage polarization","volume":"4","author":"Byles","year":"2013","journal-title":"Nat Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"17414","DOI":"10.1073\/pnas.0809136105","article-title":"Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation","volume":"105","author":"Choo","year":"2008","journal-title":"Proc Natl Acad Sci USA."},{"key":"B28","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1128\/CVI.00349-16","article-title":"In vitro experimental model of trained innate immunity in human primary monocytes","volume":"23","author":"Bekkering","year":"2016","journal-title":"Clin Vaccine Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1251086","DOI":"10.1126\/science.1251086","article-title":"Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity","volume":"345","author":"Saeed","year":"2014","journal-title":"Science."},{"key":"B30","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.immuni.2008.08.012","article-title":"The TSC-mTOR signaling pathway regulates the innate inflammatory response","volume":"29","author":"Weichhart","year":"2008","journal-title":"Immunity."},{"key":"B31","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/cr.2015.68","article-title":"Metabolic reprogramming in macrophages and dendritic cells in innate immunity","volume":"25","author":"Kelly","year":"2015","journal-title":"Cell Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1055\/s-0035-1562925","article-title":"Inflammatory characteristics of monocytes from pediatric patients with tuberous sclerosis","volume":"46","author":"Meyer","year":"2015","journal-title":"Neuropediatrics."},{"key":"B33","doi-asserted-by":"publisher","first-page":"85365","DOI":"10.18632\/oncotarget.13378","article-title":"TSC loss distorts DNA replication programme and sensitises cells to genotoxic stress","volume":"7","author":"Pai","year":"2016","journal-title":"Oncotarget."},{"key":"B34","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.tibs.2018.09.018","article-title":"The mTOR independent function of Tsc1 and FNIPs","volume":"43","author":"Sager","year":"2018","journal-title":"Trends Biochem Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1189\/jlb.2MA0117-019R","article-title":"Involvement of cell surface 90 kDa heat shock protein (HSP90) in pattern recognition by human monocyte-derived macrophages","volume":"102","author":"Bzowska","year":"2017","journal-title":"J Leukoc Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/icb.2017.13","article-title":"Evaluation of trained immunity by beta-1, 3 (d)-glucan on murine monocytes in vitro and duration of response in vivo","volume":"95","author":"Garcia-Valtanen","year":"2017","journal-title":"Immunol Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"400","DOI":"10.3390\/jcm7110400","article-title":"Shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease)","volume":"7","author":"Bermejo-Martin","year":"2018","journal-title":"J Clin Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.coi.2013.05.002","article-title":"mTOR and lymphocyte metabolism","volume":"25","author":"Zeng","year":"2013","journal-title":"Curr Opin Immunol."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.01515\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T04:24:25Z","timestamp":1596774265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.01515\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2020.01515"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.01515","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]},"article-number":"1515"}}