Cancer Center Amsterdam, Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands.
Immunobiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Cell Rep. 2018 Feb 6;22(6):1484-1495. doi: 10.1016/j.celrep.2018.01.021.
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.
脾脏 CD169 巨噬细胞位于边缘区，能够有效地捕获血液传播的病原体。在这里，我们研究了 CD169 巨噬细胞结合的抗原（Ags）诱导 CD8 T 细胞反应的要求。在 Ag 靶向 CD169 巨噬细胞时，我们表明 BATF3 依赖性 CD8α 树突状细胞（DCs）对于 DNGR-1 介导的 CD8 T 细胞反应的交叉呈递至关重要。此外，我们证明参与细胞间接触的唾液酸结合凝集素 CD169 优先结合 CD8α DCs，并且 Ag 转移到 CD8α DCs 并随后激活 T 细胞依赖于 CD169 的唾液酸结合能力。最后，功能性 CD169 介导了对改良安卡拉病毒感染的有效 CD8 T 细胞反应。总之，这些数据表明，CD169 巨噬细胞和 CD8α DCs 之间的协作促进了 CD8 T 细胞反应的启动，这是通过 CD169 与 CD8α DCs 上含唾液酸的配体结合实现的。
