Inhibiting IL-10 signaling in the secondary response enhances lung inflammation. (A) Schematic for IL-10 receptor blockade during secondary infection. Memory mice were treated with anti(α)-IL-10R or isotype control antibody at the time of secondary heterosubtypic influenza challenge. (B) Weight loss morbidity (mean ± SD) throughout the course of infection for mice treated with αIL-10R (purple) or IgG isotype control (blue). Data are compiled from three independent experiments (n = 28–29 mice/group). Statistical significance was determined by two-way ANOVA. (C) Quantification of lung viral titers at indicated dpi. Data are representative of two independent experiments (n = 9 mice per condition and time point). Statistical significance was determined by two-way ANOVA. (D) Lung histopathology from mice undergoing secondary infection treated with either IgG isotype control (left) or αIL-10R antibody (right) shown in representative H&E-stained images. Scale bars correspond to 300 µM. (E) Quantification of lung inflammation from images (see Materials and methods) by average lesion size (left) and percent tissue inflammation (right) at 2 and 5 wkpi. Data are representative of three experiments (n = 14–18 mice per condition at 2 wkpi and n = 9–10 mice per condition at 5 wkpi). Statistical significance was determined by the Student’s t test. ****P ≤ 0.0001; ***P ≤ 0.001; **P ≤ 0.01; *P ≤ 0.05; ns, not significant.