{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:52:40Z","timestamp":1790776360879,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cell metabolism now appears as an essential regulator of immune cells activation. In particular, TLR stimulation triggers metabolic reprogramming of dendritic cells (DCs) with an increased glycolytic flux, whereas inhibition of glycolysis alters their functional activation. The molecular mechanisms involved in the control of glycolysis upon TLR stimulation are poorly understood for human DCs. TLR4 activation of human monocyte-derived DCs (MoDCs) stimulated glycolysis with an increased glucose consumption and lactate production. Global hexokinase (HK) activity, controlling the initial rate-limiting step of glycolysis, was also increased. TLR4-induced glycolytic burst correlated with a differential modulation of HK isoenzymes. LPS strongly enhanced the expression of HK2, whereas HK3 was reduced, HK1 remained unchanged, and HK4 was not expressed. Expression of the other rate-limiting glycolytic enzymes was not significantly increased. Exploring the signaling pathways involved in LPS-induced glycolysis with various specific inhibitors, we observed that only the inhibitors of p38\u2013MAPK (SB203580) and of HIF-1\u03b1 DNA binding (echinomycin) reduced both the glycolytic activity and production of cytokines triggered by TLR4 stimulation. In addition, LPS-induced HK2 expression required p38-MAPK\u2013dependent HIF-1\u03b1 accumulation and transcriptional activity. TLR1\/2 and TLR2\/6 stimulation increased glucose consumption by MoDCs through alternate mechanisms that are independent of p38\u2013MAPK activation. TBK1 contributed to glycolysis regulation when DCs were stimulated via TLR2\/6. Therefore, our results indicate that TLR4-dependent upregulation of glycolysis in human MoDCs involves a p38-MAPK\u2013dependent HIF-1\u03b1 accumulation, leading to an increased HK activity supported by enhanced HK2 expression.<\/jats:p>","DOI":"10.4049\/jimmunol.1701522","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T11:44:44Z","timestamp":1532346284000},"page":"1510-1521","source":"Crossref","is-referenced-by-count":85,"title":["Toll-like Receptor 4\u2013Induced Glycolytic Burst in Human Monocyte-Derived Dendritic Cells Results from p38-Dependent Stabilization of HIF-1\u03b1 and Increased Hexokinase II Expression"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-6733","authenticated-orcid":false,"given":"Laure","family":"Perrin-Cocon","sequence":"first","affiliation":[{"name":"Centre International de Recherche en Infectiologie, Biologie Cellulaire des Infections Virales, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Aublin-Gex","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, Biologie Cellulaire des Infections Virales, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Diaz","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, Biologie Cellulaire des Infections Virales, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1981-7155","authenticated-orcid":false,"given":"Christophe","family":"Rami\u00e8re","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, Biologie Cellulaire des Infections Virales, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Peri","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca , 20126 Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-7395","authenticated-orcid":false,"given":"Patrice","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, Biologie Cellulaire des Infections Virales, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Lotteau","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, Biologie Cellulaire des Infections Virales, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,1]]},"reference":[{"key":"2025030417572346800_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. 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