Fig. 1: Gsdmd disruption alleviates C. albicans infection and associated kidney damage. | Nature Communications

Fig. 1: Gsdmd disruption alleviates C. albicans infection and associated kidney damage.

From: Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages

Fig. 1

a C. albicans-triggered GSDMD cleavage in mouse bone marrow-derived macrophages (BMDMs). BMDMs from WT (C57BL/6 J) or Gsdmd-/- (C57BL/6 J) mice were untreated or infected with WT C. albicans for 6 h at MOI 50. Full-length (p53) GSDMD, cleaved (p30) GSDMD, pro-caspase-1, and cleaved caspase-1 in the cell lysates were detected by western blotting. The figure shows the result of a representative experiment that was repeated three times. Source data are provided as a Source Data file. b Kaplan-Meier survival plots of C. albicans-challenged WT (n = 15) and Gsdmd-/- (n = 15) mice. Age- and sex-matched (10-week-old female) WT and Gsdmd-/- mice were intravenously challenged with 2 × 105 CFU C. albicans and monitored for 15 days. Survival rates were analyzed using Kaplan-Meier survival curves and log-rank testing (p = 0.0031 vs. WT). c Comparison of body weight changes of C. albicans-challenged WT and Gsdmd-/- mice. Two-tailed unpaired Student’s t test was used for statistical comparisons. Data presented are the means ± SD (n = 9 for WT, n = 4 for Gsdmd-/-) of 3 independent experiments. p = 0.0443 vs. WT at day 10. d Clinical score of C. albicans-challenged WT and Gsdmd-/- mice. Data presented are the means ± SD (n = 7 mice per data point) of three independent experiments. Comparison was made by two-way ANOVA followed by Sidak’ multiple comparisons test. p = 0.0443 (12 h), p < 0.0001 (24 h) vs. WT. e Comparison of the kidneys of C. albicans-challenged WT and Gsdmd-/- mice. Mice were sacrificed 2 weeks after the C. albicans infection. Shown are representative images from three independent experiments. f Kidney weights of C. albicans-challenged WT and Gsdmd-/- mice. Two-tailed unpaired Student’s t test was used for statistical comparisons. Data presented are the means ± SD (n = 8 kidneys per group) of three independent experiments. p = 0.012 (Challenged) vs. WT. g Kidney weights are shown as the weight per gram body weight of each mouse. Two-tailed unpaired Student’s t test was used for statistical comparisons. Data presented are the means ± SD (n = 8 kidneys per group) of three independent experiments. p = 0.0049 (Challenged) vs. WT. h Histopathologic assessment of the kidneys of WT and Gsdmd-/- mice 2 days after intravenous injection of 1 × 106 CFU C. albicans. Shown are representative H&E-stained sections of kidney tissues from three independent experiments. i Fungal burden in the kidneys, livers, spleens, and lungs of WT and Gsdmd-/- mice. Mice were sacrificed 2 days after intravenous injection of 1 × 106 CFU C. albicans. Whole organs were homogenized, and live C. albicans in the indicated organs were quantified as CFU per tissue. Data presented are the means ± SD (n = 7 mice per group) of three independent experiments. Comparison was made by two-way ANOVA followed by Sidak’ multiple comparisons test. p < 0.0001 (kidney) vs. WT. j C. albicans in the kidneys were identified by Grocott methenamine silver staining. Mice were sacrificed 2 days after intravenous injection of 1 × 106 CFU C. albicans. The figure shows the result of a representative experiment that was repeated three times.

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