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

Front Immunol. 2021 Jul 28;12:697840. doi: 10.3389/fimmu.2021.697840. eCollection 2021.

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 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.

Keywords: CD169; CD8+ T cell; COVID-19; Siglec-1; antigen-presentation; cancer; monocyte; nanovaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology
  • Carcinoma, Pancreatic Ductal / immunology
  • Cells, Cultured
  • Flow Cytometry
  • Humans
  • Influenza, Human / immunology
  • Interferon-alpha / pharmacology
  • Lipopolysaccharide Receptors / metabolism
  • Lung Neoplasms / immunology
  • Lymphocyte Activation / immunology*
  • Monocytes / immunology*
  • Pancreatic Neoplasms / immunology
  • SARS-CoV-2 / immunology
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism*

Substances

  • CD14 protein, human
  • IFNA1 protein, human
  • Interferon-alpha
  • Lipopolysaccharide Receptors
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1