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

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 sh...

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Veröffentlicht in:Nature communications 2021-07, Vol.12 (1), p.4567-4567, Article 4567
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24807-0