Fig. 3: SARS-CoV-2-induced generation of Slamf9⁺ macrophages for viral clearance.

a The number of total Slamf9⁺ macrophages, the proportion of virus-positive Slamf9⁺ macrophages, and their proportion in total virus-positive cells at each timepoint. b Left, bar chart showing the proportion of Slamf9⁺ macrophages and proliferating Slamf9⁺ macrophages in total lung cells detected in two replicated hamsters by scRNA-seq. Right, boxplot showing the proportion of Slamf9⁺ macrophages and proliferating Slamf9⁺ macrophages in total Stereo-seq bin80-bins of nine lung slides at each timepoint. Data are represented as mean ± SEM (n = 9 slides per timepoint). Center line, median; box bounds, first and third quartiles; whiskers, 1.5 times the interquartile range. Kruskal–Wallis test. c Representative images of the lung sections of hACE2 mice before and after SARS-CoV-2 infection detected by immunofluorescent staining. SLAMF9, SPP1 and CD68 at d0 and d7. SLAMF9⁺SPP1⁺ macrophages were indicated by arrows. Scale bars, 50 μm. d Boxplot showing the spatial correlation between different cell types and Slamf9⁺ macrophages of nine lung slides at d2, d5 and d7. Data are represented as mean ± SEM (n = 9 slides per timepoint). Center line, median; box bounds, first and third quartiles; whiskers, 1.5 times the interquartile range. Kruskal–Wallis test was performed to calculate the P value across different timepoints. Pearson correlation was performed to calculate the P value of all spots within each slide. Black dots: P < 0.05; gray dots: P ≥ 0.05. Red dotted line represents the correlation value of 0. e Representative interaction pathways among Slamf9⁺ macrophages, proliferating Slamf9⁺ macrophages and neurtophils subpopulations. The initiation of the chord represented the source subpopulations, and the end of the chord represented the targeted subpopulations. f Spatial expression of representative paired ligand–receptor genes, represented by a lung section at d7. Scale bars, 2 mm. g Relative mRNA expression level of Slamf9, IAV copies and Ifnb1 detected in the SLAMF9^hi and SLAMF9^lo macrophages in the lung tissues of C57BL/6 J mice at 5 days after IAV infection. Unpaired two-sided Student’s t-tests (n = 3 independent experiments). *P < 0.05, **P < 0.01, ****P < 0.0001.