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.