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

Dieke van Dinther, Henrike Veninga, Salvador Iborra, Ellen G F Borg, Leoni Hoogterp, Katarzyna Olesek, Marieke R Beijer, Sjoerd T T Schetters, Hakan Kalay, Juan J Garcia-Vallejo, Kees L Franken, Lamin B Cham, Karl S Lang, Yvette van Kooyk, David Sancho, Paul R Crocker, Joke M M den Haan

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Pages (from-to)1484-1495
Number of pages12
JournalCell Reports
Volume22
Issue number6
DOIs
Publication statusPublished - 6 Feb 2018

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