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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Lymphocyte Activation / immunology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Sialic Acid Binding Ig-like Lectin 1 / immunology*

Substances

  • Sialic Acid Binding Ig-like Lectin 1