Fig. 8: pDCs are not required for the resistance to SARS-CoV-2 infection and can be detrimental.

a–c, K18:hACE transgenic mice bred or not with indicated mutant mice were infected with 200 p.f.u. (i.n.). of SARS-CoV-2 strain. Survival was evaluated using Kaplan–Meier plots analyzed with a log-rank (Mantel–Cox) test. n = 28 female K18:hACE and K18:hACE pDC-less; 19 male K18:hACE, 26 male K18:hACE pDC-less (a), n = 10 K18:hACE and plain Ifnar1^KO, 15 K18:hACE Ifnar1^KO (b) and n = 12 female K18:hACE, 9 female K18:hACE Tlr7^KO; 11 male K18:hACE, 7 male K18:hACE Tlr7^KO (c). d, Normalized expression (log₂) of the indicated genes based on bulk RNA-seq samples obtained by whole lung samples isolated from transgenic K18:hACE mice infected with 1.1 × 10⁵ p.f.u. of SARS-CoV-2 at the indicated days p.i. Data (mean ± s.e.m.) shown are from n = 3 at 0 and 1, 5 at 2 and 4, 2 at 6 days p.i. e,f, Percentages of pDCs (e) and YFP⁺ pDCs (f, IFN-producing pDCs) within lung CD45⁺ cells of K-18:hACE SCRIPT mice infected with 1.1 × 10⁵ p.f.u. of SARS-CoV-2. n = 10 females (F) at 0, 8F and 4 males (M) at 1, 7F at 2 and 9F and 4M at 4 days p.i. g, Expression of indicated genes were analyzed by RT–qPCR in lungs of SARS-CoV-2-infected CTR, pDC-less and Tlr7^KO K18:hACE mice during infection. Data were normalized to Actin expression. Data (mean + s.e.m.) are from two independent experiments (7F and 2M CTR, 5F and 2M pDC-less, 4F and 2M Tlr7^KO at 0, 5F and 5M CTR, 7F and 5M pDC-less, 6F and 5M Tlr7^KO at 2, 6F and 6M for each strain at 4 days p.i.). A nonparametric one-way ANOVA (Kruskal–Wallis test followed by Dunn’s post hoc test) was used in d–f. A two-way ANOVA with Tukey’s multiple comparison test was used in g.

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