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. 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

Extended data figure 1. Targeting viral replication and the downstream interferon response attenuates the hyperactive immune/inflammatory response (matched to figure 1).

Extended data figure 1.

a. Representative gating strategy of human immune cells in the lungs of SARS-CoV-2 infected MISTRG6-hACE2 mice. Cells isolated from lungs or bronchioalveolar lavage (BAL) were stained with antibodies against human CD45, HLA-DR, CD68, CD16, CD14, CD206, CD86, CD11B, CD11C, CD123, CD3, and mouse CD45. Cell numbers were calculated using counting beads.

b. Human immune cells (numbers) in BAL (14dpi) or lungs (14 and 28dpi) of SARS-Cov-2 infected MISTRG6-hACE2 mice treated with dexamethasone (Dex), Remdesivir (RDV), anti-IFNAR2 or a combined therapy of Remdesivir (RDV) and anti-IFNAR2. 14dpi, BAL: CTRL-infected n=5, Dex; RDV anti-IFNAR2 n=3; anti-IFNAR2+RDV n=4 biologically independent mice examined over 2 independent experiments. 14dpi, Lung: CTRL-infected n=7; Dex, RDV, anti-IFNAR2, anti-IFNAR2+RDV n=4 biologically independent mice examined over 3 independent experiments. 28dpi, lung: CTRL infected n=5, Dex n=4, RDV n=3, anti-IFNAR2 n=3, anti-IFNAR2+RDV n=6 biologically independent mice examined over 3 independent experiments. Means with individual datapoints plotted. Unpaired, two-tailed t-test. P<0.0001=8.19×10−5.

c. Representative flow cytometry plots and frequencies of alveolar macrophages (AMs) (middle: hCD206hihCD86+hCD68+) or inflammatory macrophages (bottom: hCD206lo/−hCD86+hCD68+) in 14dpi or 28dpi lungs of treated or untreated MISTRG6-hACE2 mice. 14dpi: CTRL infected n=5, Dex n=4, RDV n=4, anti-IFNAR2 n=4, anti-IFNAR2+RDV n=4 biologically independent mice examined over at least 2 independent experiments. 28dpi: CTRL infected n=5, Dex n=4, RDV n=3, anti-IFNAR2 n=3, anti-IFNAR2+RDV n=6 biologically independent mice examined over 3 independent experiments. Means with individual datapoints. Unpaired, two-tailed t-test. P<0.0001=4.67×10−5.

d. Frequencies (left) and numbers (right) of lung pDCs at 14dpi. CTRL-infected n=6, Dex n=4, RDV, anti-IFNAR2 n=3, anti-IFNAR2+RDV n=6 mice examined over at least 2 experiments. Means with datapoints. Unpaired, two-tailed t-test. P<0.0001=7.29×10−5.

e. IFNA transcript levels measured by qPCR in treated or control untreated MISTRG6-hACE2 mice infected with SARS-CoV-2: Uninfected n=5; CTRL infected: 4dpi n=8, 14dpi n =9, 28dpi n=: 6; Dex 14dpi n=4, Dex 28dpi= 4; RDV 14 and 28dpi n=3, anti-IFNAR2 14 and 28dpi n=3, anti-IFNAR2+ Remdesivir 14 and 28dpi n=4 biologically independent mice examined over at least 2 independent experiments. Normalized to HPRT1. Violin plots with individual datapoints. Unpaired, two-tailed t test.

f. Representative histograms and frequencies of HLA-DR+ activated T cells in treated or control mice. 14dpi: CTRL-infected n=5, Dex, RDV, anti-IFNAR2, anti-IFNAR2+RDV n=4; 28dpi: CTRL infected, Dex, anti-IFNAR2+RDV n=4, RDV, anti-IFNAR2 n=3 biologically independent mice examined over 3 independent experiments. Means with datapoints. Unpaired, two-tailed t-test.

Some of the data associated with dexamethasone therapy used here as a control have been reported19.