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

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 CD8 alpha(+) 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 CD8 alpha(+) DCs and that Ag transfer to CD8 alpha(+) 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 CD8 alpha(+) DCs for the initiation of effective CD8(+) T cell responses is facilitated by binding of CD169 to sialic acid containing ligands on CD8 alpha(+) DCs.