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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.

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