{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:58:10Z","timestamp":1780574290925,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T00:00:00Z","timestamp":1569456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The 3\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010desacyl\u20104\u2019\u2010monophosphoryl lipid A (MPL) activates immunity through Toll\u2010like receptor 4 (TLR4) signaling. The Adjuvant System AS01 contains MPL and is used in the candidate malaria vaccine and the licensed zoster vaccine. Recent studies reported that AS01 adjuvant activity depends on a transient inflammation at the site of vaccination, but the role of stromal or structural cells in the adjuvant effect is unknown. We investigated this question in mouse models by assessing the role of TLR4 on hematopoietic versus resident structural cells during immunization with AS01\u2010adjuvanted vaccines. We first established that TLR4\u2010deficient animals had a reduced immune response to an AS01\u2010adjuvanted vaccine. Using bone marrow chimera, we consistently found that\n                    <jats:italic>Tlr4<\/jats:italic>\n                    expression in radio\u2010sensitive cells, i.e., hematopoietic cells, was required for an optimal adjuvant effect on antibody and T\u2010cell responses. At day 1 after injection, the pro\u2010inflammatory reaction at the site of injection was strongly dependent on TLR4 signaling in hematopoietic cells. Similarly, activation of dendritic cells in muscle\u2010draining lymph nodes was strictly associated with the radio\u2010sensitive cells expressing\n                    <jats:italic>Tlr4<\/jats:italic>\n                    . Altogether, these data suggest that MPL\u2010mediated TLR4\u2010signaling in hematopoietic cells is critical in the mode of action of AS01.\n                  <\/jats:p>","DOI":"10.1002\/eji.201948234","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T20:14:58Z","timestamp":1567714498000},"page":"2134-2145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Toll\u2010like receptor 4 signaling in hematopoietic\u2010lineage cells contributes to the enhanced activity of the human vaccine adjuvant AS01"],"prefix":"10.1002","volume":"49","author":[{"given":"Laurye","family":"Van Maele","sequence":"first","affiliation":[{"name":"Institut Pasteur de Lille Univ. Lille, CNRS, Inserm, CHU Lille  U1019 \u2010 UMR 8204 \u2010 CIIL \u2010Centre d'Infection et d'Immunit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Fougeron","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Lille Univ. Lille, CNRS, Inserm, CHU Lille  U1019 \u2010 UMR 8204 \u2010 CIIL \u2010Centre d'Infection et d'Immunit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Cayet","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Lille Univ. Lille, CNRS, Inserm, CHU Lille  U1019 \u2010 UMR 8204 \u2010 CIIL \u2010Centre d'Infection et d'Immunit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Chalon","sequence":"additional","affiliation":[{"name":"GSK  B\u20101330 Rixensart Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Piccioli","sequence":"additional","affiliation":[{"name":"GSK  B\u20101330 Rixensart Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Collignon","sequence":"additional","affiliation":[{"name":"GSK  B\u20101330 Rixensart Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Claude","family":"Sirard","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Lille Univ. 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