TY - JOUR
T1 - CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity
AU - Affandi, Alsya J.
AU - Olesek, Katarzyna
AU - Grabowska, Joanna
AU - Nijen Twilhaar, Maarten K.
AU - Rodríguez, Ernesto
AU - Saris, Anno
AU - Zwart, Eline S.
AU - Nossent, Esther J.
AU - Kalay, Hakan
AU - de Kok, Michael
AU - Kazemier, Geert
AU - Stöckl, Johannes
AU - van den Eertwegh, Alfons J.M.
AU - de Gruijl, Tanja D.
AU - Garcia-Vallejo, Juan J.
AU - Storm, Gert
AU - van Kooyk, Yvette
AU - den Haan, Joke M.M.
N1 - Funding Information:
This work was supported by grants from the Dutch Cancer Society (VU2016-10449, VU2019-12802) to JH, YK, TG, and (VU2019-12802) to AE, from the Phospholipid Research Center to JH and YK (JDH-2020-082/1-1), from NWO ZonMW (TOP 91218024) to JH and GS, and de Bennink and Cancer Center Amsterdam Foundations to GK.
Publisher Copyright:
© 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.
PY - 2021/7/28
Y1 - 2021/7/28
N2 - 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.
AB - 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.
KW - antigen-presentation
KW - cancer
KW - CD169
KW - CD8 T cell
KW - COVID-19
KW - monocyte
KW - nanovaccine
KW - Siglec-1
UR - http://www.scopus.com/inward/record.url?scp=85112435869&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.697840
DO - 10.3389/fimmu.2021.697840
M3 - Article
C2 - 34394090
AN - SCOPUS:85112435869
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 697840
ER -