Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection. A longitudinal analysis of SARS-CoV-2 infection in humans is challenging. Here the authors show a single cell RNA-sequencing analysis of BAL fluid cells from ferrets and characterise the time dependent recruitment of macrophage subsets to the lungs in response to SARS-CoV-2 infection.
【저자키워드】 SARS-CoV-2, viral infection, Monocytes and macrophages, 【초록키워드】 Macrophage, immune response, Gene Expression, macrophages, Inflammatory responses, SARS-COV-2 infection, Human, drugs, lung, Single-cell RNA sequencing, Characteristics, Bronchoalveolar lavage fluid, ferret, trajectory, Single Cell, recruitment, change, RNA-sequencing, longitudinal analysis, Analysis, Activation, landscape, ferrets, immune microenvironment, subpopulation, approach, Cell, identify, proportion, changes in, reveal, subset, infiltrating, downregulated, days post-infection, uninfected control, M2 macrophage, transcriptome change, 【제목키워드】 Transcriptome, Macrophage, SARS-COV-2 infection, Bronchoalveolar lavage fluid, ferret, reveal,