Figure 7.
Paracrine amplification of the IFN response is predicted by the model and verified experimentally. (A) Comparison between model and experiment for low infection doses. For low viral doses yielding sparse infection (1, 2, and 5 HAU/ml), the model predicts IFN response kinetics of the correct magnitude (solid lines, model; dots, experimental data). (B) Paracrine propagation of the signal. The rarity of IFN-β-producing cells at low infection doses reveals strong paracrine propagation of the IFN response because up to ∼40 times as many cells respond with IRF-7–mCherry expression (IFN responders). The agreement between model (squares) and experimental data (black dots) is remarkable, given that the model was calibrated only for a single condition (40 HAU/ml, marked with blue square) while the red squares represent predictions that were subsequently tested. (C) Co-culture of IFN-β–tGFP (green) and IRF-7–mCherry (red) cells illustrates paracrine communication. IFN-β–tGFP reporter cells were infected with 40 HAU/ml NDV for 1 h. Then IRF-7–mCherry cells were added at same density and cells were subjected to time-lapse microscopy. Merged fluorescent pictures for IFN-β–tGFP and IRF-7–mCherry at selected time points post-infection are shown. Source data is available for this figure in the Supplementary Information.
