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.
【저자키워드】 COVID-19, Cancer, monocyte, CD169, CD8+ T cell, nanovaccine, antigen-presentation, Siglec-1, 【초록키워드】 Treatment, Monocytes, Inflammatory responses, T cells, interferon, peptide, CD8, dendritic cells, flow cytometry, Antigen, Protein, T cell, Health, Bronchoalveolar lavage fluid, cancers, Patient, phenotype, expression, patients, COVID-19 patients, Blood, IFNα, CD16, Analysis, antigen-presenting cell, APCS, Activation, increased expression, CD14, inflammatory conditions, different diseases, HLA molecules, approach, WT1, defined, described, classical, investigated, evaluated, activated, expressed, upregulated, activate, stimulatory, 【제목키워드】 CD8, Capacity, CD14, enhanced,