Figure 7.

Stage-Specific Role of pDCs, Macrophages, and cDCs in Generating IFN-α/β-Induced Protective Immunity

(A) Schematic figure to show cell depletion at different stages of IFN-α/β cytokine production after YM infection.

(B and C) Depletion of pDCs in Mavs^−/− mice by anti-mPDCA-1 antibody administrated at 24 hr before or 24 hr after YM infection. Serum amounts of IFN-α/β collected at 24 hr after infection are shown in (B). Daily YM parasitemias and mortality rates are shown in (C).

(D and E) Depletion of macrophages in Tmem173^gt mice by clodronate (700 μg/injection) administered 2 days before or 1 day after YM infection. Control liposome served as a control. Serum amounts of IFN-α/β collected at 24 hr after YM infection in Tmem173^gt mice untreated (control liposome) or treated with clodronate at the indicated times are shown in (D). Parasitemias and mortality rates are shown in (E).

(F and G) WT chimeric mice were irradiated and transplanted with bone marrow cells of Mavs^−/−:Zbtb46-DTR mice, then untreated or treated with DT as indicated at 4 days before or 1 day after YM infection. Serum amounts of IFN-α/β collected at 24 hr after infection are shown in (F), and daily YM parasitemias and mortality rates are shown in (G).

(H and I) WT and Rag2^−/− mice were infected with YM, followed by i.v. administration of recombinant mouse IFN-α/β at 18 hr post infection. Parasitemias at day 5 and day 7 are shown in (H). Daily YM parasitemias and mortality rates are shown in (I).

(J and K) Intracellular staining of IFN-γ were measured by flow cytometry in splenocytes of WT and Mavs^−/− mice at day 10 post YM infection, followed by stimulation with crude antigens (YM iRBCs). Statistical analysis is shown in (J). Meanwhile, splenocytes from YM-infected WT and Mavs^−/− mice were cultured with crude antigens (iRBCs) overnight, and cell supernatants were collected for ELISA analysis (K).

(L) Malaria specific IgG in serum from WT and Mavs^−/− mice at day 10 post YM infection, evaluated by ELISA.

Data are representative of three independent experiments and are plotted as the mean ± SD. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001 versus corresponding control. NS, not significant. † denotes mouse death.

See also Figure S7.