Fig. 5: IFN-I produced by pDCs during IAV infection are deleterious.

a, Scheme illustrating the generation of pDC-SBMC mice. Only the hind limbs of pDC-less mice were irradiated, while the rest of the body was protected by a lead shield (gray oval). Upon local irradiation-induced distress, donor BM cells preferentially reconstituted immune cell types absent in the recipient (pDCs). b, Recipient CD45.1⁺ (gray) pDC-less mice are used as recipients of pDC-SBMC reconstituted with donor CD45.2⁺ (black) BM cells. The percentage of donor (black) versus recipient (gray) cells was analyzed in indicated lineages 4 weeks after reconstitution (n = 4). c–e, pDC-SBMC mice reconstituted with CTR, pDC-less or Myd88^KO BM (c), with CTR or Tlr7^KO BM (d) or with CTR, pDC-less or Irf7^KO (e) were infected (i.n.) with 145 p.f.u. of IAV strain and monitored daily to assess their morbidity and survival. Kaplan–Meier survival plots show the percentages of survival of indicated genotypes. c,d, Pool of two independent experiments (8 CTR, 7 Myd88^KO and 10 pDC-less SBMC in c; 8 CTR and 9 Tlr7^KO SBMC in d). e, Pool of three independent experiments (n = 12 for each SBMC type). A log-rank (Mantel–Cox) test was used for statistical analysis in c–e. f, Expression of indicated genes was analyzed by RT–qPCR in lungs isolated from indicated IAV-infected SBMC 3 days after infection (n = 4 for each strain). A nonparametric one-way ANOVA (Kruskal–Wallis test followed by Dunn’s post hoc test) was used for statistical analysis. g, Cytometric bead arrays was performed to quantify IFNα and IFNβ concentrations in the BAL isolated from the same SBMC mice used in f. Data in f,g are presented as mean ± s.e.m. Each dot represents an individual. n = 4 in f,g.

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