Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets

• Published in: Nature communications Vol. 12; no. 1; p. 4567
• Main Authors: Lee, Jeong Seok, Koh, June-Young, Yi, Kijong, Kim, Young-Il, Park, Su-Jin, Kim, Eun-Ha, Kim, Se-Mi, Park, Sung Ho, Ju, Young Seok, Choi, Young Ki, Park, Su-Hyung
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/91; 631/250/2504/342; 631/250/255/2514; 631/326/596/4130; Alveoli; Animal models; Animals; Bronchoalveolar Lavage Fluid; Bronchus; COVID-19 - genetics; COVID-19 - metabolism; Ferrets; Gene expression; Gene sequencing; Humanities and Social Sciences; Immune response; Immune system; Immunomodulation; Immunosuppressive agents; Infections; Inflammation; Lavage; Lungs; Macrophages; Macrophages - metabolism; Macrophages - physiology; Microenvironments; Monocytes; multidisciplinary; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sequence analysis; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Subpopulations; Trajectory analysis; Transcriptomes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24807-0

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.