{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:15:32Z","timestamp":1790630132171,"version":"4.1.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["VU2016-10449"],"award-info":[{"award-number":["VU2016-10449"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011748","name":"Phospholipid Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011748","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017636","name":"Cancer Center Amsterdam","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Monocytes are antigen-presenting cells (APCs) that play diverse roles in promoting or regulating inflammatory responses, but their role in T cell stimulation is not well defined. In inflammatory conditions, monocytes frequently show increased expression of CD169\/Siglec-1, a type-I interferon (IFN-I)-regulated protein. However, little is known about the phenotype and function of these CD169<jats:sup>+<\/jats:sup> monocytes. Here, we have investigated the phenotype of human CD169<jats:sup>+<\/jats:sup> monocytes in different diseases, their capacity to activate CD8<jats:sup>+<\/jats:sup> T cells, and the potential for a targeted-vaccination approach. Using spectral flow cytometry, we detected CD169 expression by CD14<jats:sup>+<\/jats:sup> CD16<jats:sup>-<\/jats:sup> classical and CD14<jats:sup>+<\/jats:sup> CD16<jats:sup>+<\/jats:sup> intermediate monocytes and unbiased analysis showed that they were distinct from dendritic cells, including the recently described CD14-expressing DC3. CD169<jats:sup>+<\/jats:sup> monocytes expressed higher levels of co-stimulatory and HLA molecules, suggesting an increased activation state. IFN\u03b1 treatment highly upregulated CD169 expression on CD14<jats:sup>+<\/jats:sup> monocytes and boosted their capacity to cross-present antigen to CD8<jats:sup>+<\/jats:sup> T cells. Furthermore, we observed CD169<jats:sup>+<\/jats:sup> monocytes in virally-infected patients, including in the blood and bronchoalveolar lavage fluid of COVID-19 patients, as well as in the blood of patients with different types of cancers. Finally, we evaluated two CD169-targeting nanovaccine platforms, antibody-based and liposome-based, and we showed that CD169<jats:sup>+<\/jats:sup> monocytes efficiently presented tumor-associated peptides gp100 and WT1 to antigen-specific CD8<jats:sup>+<\/jats:sup> T cells. In conclusion, our data indicate that CD169<jats:sup>+<\/jats:sup> monocytes are activated monocytes with enhanced CD8<jats:sup>+<\/jats:sup> T cell stimulatory capacity and that they emerge as an interesting target in nanovaccine strategies, because of their presence in health and different diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2021.697840","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T15:00:35Z","timestamp":1627484435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":69,"title":["CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity"],"prefix":"10.3389","volume":"12","author":[{"given":"Alsya J.","family":"Affandi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Olesek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Grabowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten K.","family":"Nijen Twilhaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anno","family":"Saris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline S.","family":"Zwart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther J.","family":"Nossent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"Kalay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"de Kok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Kazemier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"St\u00f6ckl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfons J. 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