Skip to main content
. Author manuscript; available in PMC: 2022 Aug 1.
Published in final edited form as: Nature. 2022 Apr 28;606(7914):585–593. doi: 10.1038/s41586-022-04802-1

Figure 4. Inflammasome inhibition ameliorates inflammation and disease in infected MISTRG6-hACE2 mice.

Figure 4.

a. Schematic of inflammasome inhibition in vivo. SARS-CoV-2 infected MISTRG6-hACE2 mice treated with caspase-1 or NLRP3 inhibitors, 6–12dpi.

b. Frequencies of mNG+ human immune cells upon inflammasome inhibition. CTRL-infected n=5, caspase-1 inhibitor n=6, NLRP3 inhibitor n=4 mice examined over at least 2 experiments. Means with datapoints. Paired, two-tailed t-test.

c. Frequencies of CXCL10+ or TNF+ human lung macrophages upon inflammasome inhibition. CTRL-infected n=5, caspase-1 inhibitor n=5, NLRP3 inhibitor n=4 mice examined over at least 2 experiments. Means with datapoints. Unpaired, two-tailed t-test.

d. Quantification of active caspase-1 in mNG+ human macrophages upon inflammasome inhibition. CTRL-infected n=5, Casp1-inhibitor n=5, NLRP3-inhibitor n=4 mice examined over at least 2 experiments. Means with datapoints. Unpaired, two-tailed t-test.

e. Serum human IL-18 levels upon inflammasome inhibition. CTRL, NLRP3: n=4, Casp1 n=5 mice examined over 2 experiments. Means with datapoints. Unpaired, two-tailed t-test. P<0.0001=1.00114×10−5.

f. Human IL-1RA levels in lung homogenates upon inflammasome inhibition. N=4 mice examined over 2 experiments. Means with datapoints. Unpaired, two-tailed t-test.

g. Serum GSDMD levels upon inflammasome inhibition. CTRL-infected n=5, Casp1, NLRP3 inhibitors n=4 mice examined over 2 experiments. Means with datapoints. Unpaired, two-tailed t-test.

h. Box and whisker plot of histopathological scores upon inflammasome inhibition. CTRL-infected n=4, Casp1-inhibitor n=6, NLRP3-inhibitor n=4 independent mice over at least 2 experiments. Whiskers: smallest (minimum) to the largest value (maximum). Box: 25th-75th percentiles. Center line: median. Unpaired, two-tailed t-test.

i. Viral titers from supernatants of BMDMs infected with SARS-CoV-2-mNG in vitro and treated with Casp1 or NLRP3 inhibitors. CTRL-infected: n=13, Casp1-inhibitor-: n=8, NLRP3 inhibitor: n=5 independent datapoints collected over 3 experiments. Means with datapoints. Unpaired two-tailed t-test.