CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

• Main Authors: Alsya J. Affandi, Katarzyna Olesek, Joanna Grabowska, Maarten K. Nijen Twilhaar, Ernesto Rodríguez, Anno Saris, Eline S. Zwart, Esther J. Nossent, Hakan Kalay, Michael de Kok, Geert Kazemier, Johannes Stöckl, Alfons J. M. van den Eertwegh, Tanja D. de Gruijl, Juan J. Garcia-Vallejo, Gert Storm, Yvette van Kooyk, Joke M. M. den Haan
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-07-01
• Series: Frontiers in Immunology
• Subjects: monocyte; CD169; antigen-presentation; CD8+ T cell; nanovaccine; cancer
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.697840/full

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+ 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.