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Cell Rep. 2018 Feb 6;22(6):1484-1495. doi: 10.1016/j.celrep.2018.01.021.

Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming.

Author information

1
Cancer Center Amsterdam, Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands.
2
Immunobiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
3
Department of Immunohematology and Bloodtransfusion, LUMC, Leiden, the Netherlands.
4
Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.
5
Division of Cell Signalling and Immunology, University of Dundee, Dundee, UK.
6
Cancer Center Amsterdam, Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: j.denhaan@vumc.nl.

Abstract

Splenic CD169+ macrophages are located in the marginal zone to efficiently capture blood-borne pathogens. Here, we investigate the requirements for the induction of CD8+ T cell responses by antigens (Ags) bound by CD169+ macrophages. Upon Ag targeting to CD169+ macrophages, we show that BATF3-dependent CD8α+ dendritic cells (DCs) are crucial for DNGR-1-mediated cross-priming of CD8+ T cell responses. In addition, we demonstrate that CD169, a sialic acid binding lectin involved in cell-cell contact, preferentially binds to CD8α+ DCs and that Ag transfer to CD8α+ DCs and subsequent T cell activation is dependent on the sialic acid-binding capacity of CD169. Finally, functional CD169 mediates optimal CD8+ T cell responses to modified vaccinia Ankara virus infection. Together, these data indicate that the collaboration of CD169+ macrophages and CD8α+ DCs for the initiation of effective CD8+ T cell responses is facilitated by binding of CD169 to sialic acid containing ligands on CD8α+ DCs.

KEYWORDS:

CD169; DNGR-1; Sialoadhesin; Siglec-1; T cell response; antigen; cross-presentation; dendritic cell; macrophage; vaccinia

PMID:
29425504
DOI:
10.1016/j.celrep.2018.01.021
[Indexed for MEDLINE]
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