Figure 4: NLRP3 and NLRC4 are non-redundantly activated in lung infections.

C57BL/6, Nlrp3^−/− and Nlrc4^−/− mice (n=6 for all groups) were infected intranasally with live A. fumigatus conidia or P. aeruginosa and assessed for (a) fungal or bacterial growth at different dpi; (b) IL-1β production in BAL fluids (c) and lung histology at 7 dpi (periodic acid-Schiff staining) (% of neutrophils in the bronchoalveolar lavage are shown in the insets). (d) Survival, (e) fungal growth and (f) lung histology of C57BL/6 and Cftr^−/−mice infected with A. fumigatus conidia and treated with specific Nlrp3, Nlrc4 siRNA or scrambled siRNA. Fungal growth (log CFU, mean±s.d.) and histology were assessed at 7 dpi In f, periodic acid-Schiff staining and increased deposition of DNA on lung parenchyma cells on TUNEL staining. Cell nuclei were stained blue with DAPI. Representative images of two independent experiments were acquired using EVOS FL Color Imaging System with a × 40 objective for histology (Scale bar, 100 μm) and a high-resolution Microscopy Olympus DP71 using a × 20 objective for TUNEL (Scale bar, 50 μm). Data pooled from three experiments and presented as mean±s.d. for all bar graphs. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, C57BL/6 versus Nlrp3^−/−, Nlrc4^−/−or Cftr^−/−mice at different dpi (a,b) or untreated (none) versus siRNA treated mice (e), Two-way (a,b) and One-way ANOVA (e) Bonferroni post hoc test.