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

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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(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.)