Fig. 8
Pharmacological inhibition of ferroptosis mitigates CARD9 deficiency- exacerbated renal damages and ferroptosis during C. tropicalis infection. Card9−/− and WT mice were injected with C. tropicalis (2×105 CFU per mouse) via the lateral tail veins to establish disseminated candidiasis. Meanwhile, Card9−/− mice were intraperitoneally injected with DMSO (Vehicle) or ferrostatin-1 (Fer-1, 10 mg/kg) every day. (A) The mice were monitored daily for survival postinfection (n = 8). (B-H) Mice were euthanized at day 5 (n = 6). Representative photographs of kidney slices stained with hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS). Scale bar: 50 µM. And the inflammatory score and fungal burden was also calculated (B). The percentage of MDSCs (CD11b+Gr1+) in kidney, spleen and bone marrow (BM) were analyzed by flow cytometry (C and D). The levels of serum TREM1, NGAL, BUN and sCr were assessed by the corresponding assay kit (E). The protein level of 4HNE in infected kidneys was detected by immunofluorescence. 4HNE shown in red. DAPI (blue) was used to stain the nuclei. Scale bar: 50 µM (F). The relative renal MDA level was measured by MDA Assay Kit (G). The cell death in infected kidneys was determined by TUNEL staining. TUNEL staining shown in green. DAPI (blue) was used to stain the nuclei. Scale bar: 50 µM (H). Data with error bars are expressed as mean ± SEM. Each panel shows at least six independent biological replicates from a typical experiment. Statistical analysis was determined by the log-rank (Mantel-Cox) test (A) and one-way ANOVA with Bonferroni’s multiple comparisons test for post-hoc test (B-H). ns (not significant), P > 0.05; *P < 0.05, **P < 0.01, ***P < 0.001