CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity
Affandi, Alsya J; Olesek, Katarzyna; Grabowska, Joanna; Nijen Twilhaar, Maarten K; Rodríguez, Ernesto; Saris, Anno; Zwart, Eline S; Nossent, Esther J; Kalay, Hakan; de Kok, Michael; Kazemier, Geert; Stöckl, Johannes; van den Eertwegh, Alfons J M; de Gruijl, Tanja D; Garcia-Vallejo, Juan J; Storm, Gert; van Kooyk, Yvette; den Haan, Joke M M
(2021) Frontiers in Immunology, volume 12, pp. 1 - 15
(Article)
Abstract
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
... read more
of these CD169+ monocytes. Here, we have investigated the phenotype of human CD169+ monocytes in different diseases, their capacity to activate CD8+ T cells, and the potential for a targeted-vaccination approach. Using spectral flow cytometry, we detected CD169 expression by CD14+ CD16- classical and CD14+ CD16+ intermediate monocytes and unbiased analysis showed that they were distinct from dendritic cells, including the recently described CD14-expressing DC3. CD169+ monocytes expressed higher levels of co-stimulatory and HLA molecules, suggesting an increased activation state. IFNα treatment highly upregulated CD169 expression on CD14+ monocytes and boosted their capacity to cross-present antigen to CD8+ T cells. Furthermore, we observed CD169+ 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+ monocytes efficiently presented tumor-associated peptides gp100 and WT1 to antigen-specific CD8+ T cells. In conclusion, our data indicate that CD169+ monocytes are activated monocytes with enhanced CD8+ T cell stimulatory capacity and that they emerge as an interesting target in nanovaccine strategies, because of their presence in health and different diseases.
show less
Download/Full Text
Keywords: monocyte, CD169, antigen-presentation, CD8+ T cell, nanovaccine, cancer, COVID-19, Siglec-1
ISSN: 1664-3224
Publisher: Frontiers Media S.A.
Note: Copyright © 2021 Affandi, Olesek, Grabowska, Nijen Twilhaar, Rodríguez, Saris, Zwart, Nossent, Kalay, de Kok, Kazemier, Stöckl, van den Eertwegh, de Gruijl, Garcia-Vallejo, Storm, van Kooyk and den Haan.
(Peer reviewed)