CD11c+ cells played a major role in proinflammatory cytokine production in vivo. (a) Depletion of dendritic cells in CD11c-DTR mice via diphtheria toxin (DT) treatment reduced IFN-γ and IL-12 production and there was a trend toward reduced IL-6 production, in comparison to control mice [CD11c-DTR mice treated with phosphate-buffered saline (PBS) and wild-type (WT) mice treated with DT or PBS], following injection of LD. For IFN-γ and IL-12 graphs P ≤ 0.0055 by two-way analysis of variance (ANOVA) for 0- to 6-hour time points, Bonferroni post-test **P < 0.01 for CD11c-DTR+DT versus CD11c-DTR+PBS, WT+DT, and WT+PBS. (b) Depletion of NK1.1+ cells in WT mice via administration of NK1.1 depletion antibody (anti-NK1.1) reduced IFN-γ and IL-6 production to a small degree and did not affect IL-12 production, in comparison to control mice [administered mouse-IgG2a (mIgG2a) isotype control], following injection of LD vector. For IFN-γ and IL-6, P ≤ 0.04 by two-way ANOVA for 0- to 6-hour time points, (IL-12 = ns), Bonferroni post-test #P < 0.05 and ##P < 0.001 for anti-NK1.1 versus mIgG2a. Graphs show mean ± SE. IFN, interferon; IL, interleukin; LD, liposome:DNA.