Figure 6. IFNαβ derived from pDCs and other PDCA-1+ cells mediates inflammation and morbidity in infected 129S7 mice.
(a) 129S7 (open triangles), IFNαβR−/−(129) (filled triangles) or B6 (open circles) mice were infected with X31 and flow cytometric quantification of pDCs, NK cells and inflammatory monocytes in the lung was performed. 129S7:IFNαβR−/−(129) *, 129S7:B6 ○. (b–e) 129S7 mice were treated with depleting mAb αPDCA-1 or isotype control as indicated, (b) weight loss and mortality were measured, (c) IFNα protein in BAL fluid was quantified by ELISA, (d) viral titre in BAL fluid were determined and (e) cell recruitment was assessed as in a. (f) 129S7 mice were treated with depleting mAbs RB6-8C5 (filled triangles), 1A8 (open diamonds) or isotype control (open triangles) then infected with X31. (g) 129S7 mice were treated with αAsialo GM1 (filled triangles) or Vehicle Control (open triangles) then infected with X31. (f,g) Mortality and weight loss were recorded. (h) BM-derived pDCs from 129 (open columns), IFNαβR−/−(129) (checked columns) and B6 (filled columns) mice were stimulated in vitro with X31. At 24 h supernatants were collected and concentrations of IFNα, β and λ were measured by ELISA. Graphs show mean±s.e.m. and are representative of 2–3 independent experiments where n=2–4 for cellular recruitment, virus titration and ELISA, n=5–6 for weight loss and survival except for b where data are pooled from two experiments (n=12). *** or ○○○P<0.0001, ** or ○○P<0.001, *P<0.01 by two-way ANOVA with Bonferroni post tests (cell counts, weight loss and ELISA time course), Log-rank (Mantel-Cox) Test (survival) or Mann-Whitney test (pDC supernatants). The symbols on the right of graphs indicate statistical significance of the whole curve, as tested by two-way ANOVA.