van Dinther, DiekeVeninga, HenrikeIborra, SalvadorBorg, Ellen G. F.Hoogterp, LeoniOlesek, KatarzynaBeijer, Marieke R.Schetters, Sjoerd T. T.Kalay, HakanGarcia-Vallejo, Juan J.Franken, Kees L.Cham, Lamin B.Lang, Karl S.van Kooyk, YvetteSancho, DavidCrocker, Paul R.den Haan, Joke M. M.2018-11-222018-11-222018Cell Rep. 2018; 22(6):1484-14952211-1247http://hdl.handle.net/20.500.12105/6689Splenic 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacional29425504221484-149510.1016/j.celrep.2018.01.021Cell Reportsopen access