Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection
Figure 4
Treatment with IL-1RA prevents lethality in mice infected with P. chabaudi and challenged with a secondary bacterial infection.
(A) At 7 days post-infection, mice were challenged with 10 µg of LPS and serum samples collected 9 hours later for cytokine measurements. The numbers within parenthesis indicate the percentage of lethality 24 hours after low dose (10 µg/mouse) LPS challenge. (B) Splenic macrophages (CD11b+F4/80+) and DCs (CD11c+MHC-II+) from mice at 7 days post-infection were stained with FLICA reagent in order to detect active caspase-1. (C) At day 7 post-infection the mice were treated with IL-1RA (anakinra) immediately prior to LPS challenge. Lethality was assessed from 12 to 48 hours post-LPS challenge. (D) At 7 days post-infection with P. chabaudi, sub-lethal sepsis was induced by CLP. A group of mice received treatment with IL-1RA (100 mg/kg/day) beginning 24 hours before the CLP procedure. Levels of circulating IL-1β were measured 24 hs after CLP. (E) Mice received peroral challenge with 108 of Salmonella typhimurium at 5 days post-infection with P. chabaudi. A group of mice received treatment with IL-1RA (100 mg/kg/day) beginning 48 hours after bacterial challenge. The levels of circulating IL-1β were measured at 3 days post-Salmonella challenge. (F) Translocation of aerobic bacteria was quantified 24 hours after the CLP procedure. (G) Translocation of S. typhimurium was quantified 3 days after peroral challenge. We used 5 to 8 mice per group and results shown are representative of 2 independent experiments. Significant differences are *p<0.01, **p<0.005 ***p<0.001 obtained in a Chi-square test.