Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi

Figure 5

Intestinal fungi protected mice from LPS-induced sepsis through inhibiting GSDMD cleavage. (a) GSDMD cleavage of ileal tissue in water control and fluconazole-treated group 2 hours post-LPS challenge. The 53 KD and 30 KD represent the full length and N-terminal fragment of GSDMD, respectively. (b) Relative protein level of GSDMD P30 measured with Image J of (a). (c) GSDMD cleavage of ileal tissue in the SPF mice grouped as described in Figure 4(a) 2 hours post-LPS challenge. (d) Relative protein level of GSDMD P30 measured with Image J of (c). (e) Survival rate of LPS-induced sepsis in indicated groups. The Gsdmd-deficient (Gsdmd^-/-) mice were treated with water (control) or fluconazole (Fluc) for two weeks before LPS challenge. for each group. (f) The survival rate of LPS-induced sepsis in indicated groups. The GSDMD inhibitor disulfiram was administrated at the 14^th day of the water or fluconazole treated mice. per group. Mortality was compared by Kaplan-Meier survival curves and analyzed by the log-rank (Mantel-Cox) test (e, f).

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