Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming
OPEN Cell reports | 10 Feb 2018
D van Dinther, H Veninga, S Iborra, EGF Borg, L Hoogterp, K Olesek, MR Beijer, STT Schetters, H Kalay, JJ Garcia-Vallejo, KL Franken, LB Cham, KS Lang, Y van Kooyk, D Sancho, PR Crocker and JMM den Haan
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.
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