Mice deficient in all Gasdermins, or only Gasdermin D, feature elevated S.Tm CFUs in the gut tissue and in systemic organs. (A) At 48 h p.i., at least one homologue of each Gasdermin is expressed in the gut tissue. Relative expression levels of individual Gasdermins in the S.Tm infected cecum tissue of WT mice as determined by qRT-PCR. ND–Not Detected. (B) Gasdermin(s) restrict oral S.Tm gut infection. S.Tm pathogen loads in the mesenteric lymph nodes of GsdmACDE−/− mice and WT (GsdmACDE+/+) mice at 48 h p.i. (C) GSDMD is the only Gasdermin with protective function during S.Tm gut infection. S.Tm pathogen loads in mesenteric lymph nodes of littermate-controlled 48-h infections with GSDMA(A1-A3)-deficient, GSDMC(C1-C4)-deficient, GSDMD-deficient, and GSDME-deficient mice. (D–G) At 48 h p.i., GSDMD-deficient mice (GsdmD−/−) phenocopy mice deficient in all Gasdermins (GsdmACDE−/−) in terms of S.Tm pathogen loads. S.Tm pathogen loads in (D) cecum tissue, (E) mesenteric lymph nodes, (F) spleen, and (G) liver. In A, 5 mice were analyzed. Means with SD are indicated. In B–G, each data point represents one mouse. ≥5 mice per group from ≥2 independent experiments for each comparison. Line at median. The dotted line represents the detection limit. Mann-Whitney U test (ns–not significant, *P < 0.05, **P < 0.01, ***P < 0.001).