IFN-responsiveness dictates early proinflammatory macrophage maturation in the lungs of M-CoV–infected mice. (A) Significantly downregulated gene sets in lung macrophages of M-CoV–infected LysM-Cre Ifnarfl/fl compared with Ifnar-sufficient control mice. (B–D) Average expression of selected genes belonging to the indicated gene sets is projected onto t-SNE plots of macrophages from naive and M-CoV–infected control mice and infected LysM-Cre Ifnarfl/fl mice. (E) Average expression of inflammatory cytokines and chemokines in control and LysM-Cre–targeted, Ifnar-deficient macrophage clusters. (F–I) Cytokine levels of IL-1β (F), S100A8/9 (G), TNF (H), and MCP-1 (I) in the lung homogenate supernatant of LysM-Cre− LMC and LysM-Cre Ifnarfl/fl mice 2 days p.i. and naive LysM-Cre− LMC mice; means ± SEM are indicated. scRNA-seq data in (A)–(E) are representative of 10,678 macrophages. Data in (F) are representative of four independent experiments with n = 8 naive LysM-Cre− LMC mice, n = 15 M-CoV–infected LysM-Cre− LMC mice, and n = 15 M-CoV–infected LysM-Cre Ifnarfl/fl mice. Data in (G) are representative of two independent experiments with n = 5 naive LysM-Cre− LMC mice, n = 10 M-CoV–infected LysM-Cre− LMC mice, and n = 11 M-CoV–infected LysM-Cre Ifnarfl/fl mice. Data in (H) and (I) are representative of two independent experiments with n = 3 naive LysM-Cre− LMC mice, n = 7 M-CoV–infected LysM-Cre− LMC mice, and n = 6 M-CoV–infected LysM-Cre Ifnarfl/fl mice. p values in (F)–(I) as per one-way ANOVA with Tukey’s multiple comparisons test.