Gasdermin D is the only Gasdermin that provides protection against acute Salmonella gut infection in mice

Significance The host immune response against infection relies on programmed cell death that has recently been shown to involve Gasdermins—a family of membrane-pore-forming proteins. Despite abundant expression of multiple Gasdermins in mammalian gut tissue, we here find using a mouse line lacking all mouse Gasdermins at once that only Gasdermin D provides protection against oral Salmonella infection. To accomplish this protection, both gut epithelial cells and classical immune cells employ Gasdermin D to limit bacterial loads in the mucosa, to control inflammation, to prevent epithelial disruption, and to reduce systemic spread of the pathogen. Hence, this study sheds light on the differential impact of Gasdermins in infectious diseases.

Figure S1 -Supplementary figures to Fig 1

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Figure S2 -Steady state analysis Figure S2.(Steady state analysis of inflammation) (A-B) No detectable inflammatory pre-condition in the gut mucosa of GSDMD-deficient mice.(A) Microscopy-based quantification of histology scores from H&E-stained cecum tissue sections.(B) Lipocalin-2 levels of feces.In A, B, each data point represents one mouse.Line at median.Dotted line represents detection limit.(C) mRNA levels of pro-inflammatory cytokines and anti-microbial peptides.Means with SD are indicated.For all panels ≥4 mice per group.Mann-Whitney U-test (ns -not significant).

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Figure S3 -Supplementary figures to Fig 2

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Figure S5 -Supplementary figures to Fig 3

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Figure S6 -Supplementary figures to Fig 3

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Figure S7 -Supplementary figures to Fig 4 Figure S8

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Figure S9 -Supplementary figures to Fig 5