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

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.