Figure 9.

IL-1 receptor-dependent G-CSF secretion increases resistance to A. fumigatus airway infection. (A) Pulmonary fungal burden of C57BL/6, IL-1R1^-/- and IL-1R1^-/- mice treated with G-CSF (250µg of rhG-CSF, daily commencing the day of infection) following infection with A. fumigatus-containing beads. Fungal burden was measured by galactomannan EIA 3 days after infection. Results represent the mean ± SEM of groups of > 15 mice across 2 experiments, *p ≤ 0.05, **p ≤ 0.01 (one-way ANOVA test). (B) Pulmonary fungal burden of C57BL/6 mice treated with IL-1Ra with or without G-CSF (rhG-CSF) as measured by galactomannan EIA 3 days after infection with A. fumigatus beads. IL-1Ra was given at a dose of 200 µg/day intraperitoneally commencing 24 hours prior to infection and rhG-CSF was administered as in (A). Results represent the mean ± SEM of groups of > 15 mice across 2 experiments, **p ≤ 0.01 (one-way ANOVA test). (C) Total pulmonary neutrophils as determined by flow cytometry analysis of collagenase-digested lungs from the indicated mouse strains 3 days after infection with A. fumigatus-containing beads. Results represent the mean ± SEM of groups of n = 16 mice across 2 experiments, **p ≤ 0.01 (one-way ANOVA test). (D) Pulmonary ex vivo CXCL1 cytokine secretion as determined by ELISA three days after infection. Results represent mean ± SEM of groups of n ≥ 7 mice across 2 experiments, ***p ≤ 0.001 (one-way ANOVA test). Note that the data in this graph for C57BL/6 and untreated IL-1R1^-/- mice is reproduced from Figure 4a for ease of comparison as these mice were studied in the same experiments. (E) Active caspase 3 immunohistochemistry staining of lungs from C57BL/6 mice infected with A. fumigatus-containing beads and IL-1R1-/- mice infected with A. fumigatus-containing beads and treated with G-CSF. Note that this staining was done at the same time as those presented in Figure 6 and therefore for continuity it shares the same C57BL/6 image.