Subcapsular macrophages are required for NK cell activation by MVA but not by poly I:C. WT mice were treated with PBS or with clodronate (CL-Lipo) or control liposomes (PBS-Lipo) in the footpad to deplete SCS macrophages in the draining popliteal lymph node. (A-B) Depletion of CD169⁺ cells was assessed by flow cytometry 6 days after liposome treatment. Numbers correspond to percentage of cells falling in the indicated gate. (C-D) PBS-Lipo or CL-Lipo treated mice were injected with MVA (or PBS) in the footpad. (C) NK cell accumulation mediated by MVA was assessed after 24 hours. (D) Intracellular granzyme B content was measured in NK cells (NK1.1⁺ CD3⁻). Note that NK cell activation mediated by MVA was strongly reduced in CL-Lipo treated mice. (E-F) CL-Lipo–mediated depletion prevents NK cell activation by MVA but not by poly I:C. The percentage of CD69⁺ (E) and of Granzyme B^high (F) NK cells are shown for the indicated treatments and stimuli. Data are representatative of 3 independent experiments (*P < .05; **P < .01).