Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18
Fig 4
Caspase-11 controls pyroptosis of lung epithelial cells.
(A) TC-1 cells were infected with B. thailandensis or the bsaZ mutant in presence or absence of IFNγ. Active caspase-11 was pulled-down from cell lysates using Biotin-VAD-FMK and detected by immunoblot. (B) Caspase-11 expression in control (WT) and knocked-out (C11KO) TC-1 cells. (C) WT and C11KO TC-1 cells were stimulated with IFNγ (100 ng/ml) and infected with B. thailandensis (MOI 100). LDH release and intracellular bacteria replication were measured 8 hours p.i.. (D, E) Mice infected for 48 hours with B. thailandensis (5x105 CFU) were treated intranasaly with Image-iT DEAD to stain necrotic cells and euthanized. Lung histological sections were stained with anti-EpCAM antibody to visualize epithelial cells. White arrow heads indicate necrotic epithelial cells, white dots indicate live epithelial cells. One representative experiment of four (A-C) or two (D, E) is shown. *p<0.05, **p<0.01, ***p<0.001 Unpaired t-test.