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.