Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Lee JS

PROVIDER: S-EPMC8316405 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

Lee Jeong Seok JS Koh June-Young JY Yi Kijong K Kim Young-Il YI Park Su-Jin SJ Kim Eun-Ha EH Kim Se-Mi SM Park Sung Ho SH Ju Young Seok YS Choi Young Ki YK Park Su-Hyung SH

Nature communications 20210727 1

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 trans ...[more]

PMID: 34315893

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Project description:BackgroundIt is now possible to comprehensively characterize the microbiota of the lungs using culture-independent, sequencing-based assays. Several sample types have been used to investigate the lung microbiota, each presenting specific challenges for preparation and analysis of microbial communities. Bronchoalveolar lavage fluid (BALF) enables the identification of microbiota specific to the lower lung but commonly has low bacterial density, increasing the risk of false-positive signal from contaminating DNA. The objectives of this study were to investigate the extent of contamination across a range of sample densities representative of BALF and identify features of contaminants that facilitate their removal from sequence data and aid in the interpretation of BALF sample 16S sequencing data.ResultsUsing three mock communities across a range of densities ranging from 8E+ 02 to 8E+ 09 16S copies/ml, we assessed taxonomic accuracy and precision by 16S rRNA gene sequencing and the proportion of reads arising from contaminants. Sequencing accuracy, precision, and the relative abundance of mock community members decreased with sample input density, with a significant drop-off below 8E+ 05 16S copies/ml. Contaminant OTUs were commonly inversely correlated with sample input density or not reproduced between technical replicates. Removal of taxa with these features or physical concentration of samples prior to sequencing improved both sequencing accuracy and precision for samples between 8E+ 04 and 8E+ 06 16S copies/ml. For the lowest densities, below 8E+ 03 16S copies/ml BALF, accuracy and precision could not be significantly improved using these approaches. Using clinical BALF samples across a large density range, we observed that OTUs with features of contaminants identified in mock communities were also evident in low-density BALF samples.ConclusionRelative abundance data and community composition generated by 16S sequencing of BALF samples across the range of density commonly observed in this sample type should be interpreted in the context of input sample density and may be improved by simple pre- and post-sequencing steps for densities above 8E+ 04 16S copies/ml.

Project description:Proteome profile changes post-severe acute respiratory syndrome coronavirus 2 (post-SARS-CoV-2) infection in different body sites of humans remains an active scientific investigation whose solutions stand a chance of providing more information on what constitutes SARS-CoV-2 pathogenesis. While proteomics has been used to understand SARS-CoV-2 pathogenesis, there are limited data about the status of proteome profile in different human body sites infected by the SARS-CoV-2 virus. To bridge this gap, our study aims to characterize the proteins secreted in urine, bronchoalveolar lavage fluid (BALF), gargle solution, and nasopharyngeal samples and assess the proteome differences in these body samples collected from SARS-CoV-2-positive patients. We downloaded publicly available proteomic data from (https://www.ebi.ac.uk/pride/). The data we downloaded had the following identifiers: (i) PXD019423, n = 3 from Charles Tanford Protein Center in Germany. (ii) IPX0002166000, n = 15 from Beijing Proteome Research Centre, China. (iii) IPX0002429000, n = 5 from Huazhong University of Science and Technology, China, and (iv) PXD022889, n = 18 from Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905 USA. MaxQuant was used for the human peptide spectral matching using human and SARS-CoV-2 proteome database which we downloaded from the UniProt database (access date 13th October 2021). The individuals infected with SARS-CoV-2 viruses displayed a different proteome diversity from the different body sites we investigated. Overally, we identified 1809 proteins across the four sample types we compared. Urine and BALF samples had significantly more abundant SARS-CoV-2 proteins than the other body sites we compared. Urine samples had 257(33.7%) unique proteins, followed by nasopharyngeal with 250(32.8%) unique proteins. Gargle solution and BALF had 38(5%) and 73(9.6%) unique proteins respectively. Urine, gargle solution, nasopharyngeal, and bronchoalveolar lavage fluid samples have different protein diversity in individuals infected with SARS-CoV-2. Moreover, our data also demonstrated that a given body site is characterized by a unique set of proteins in SARS-CoV-2 seropositive individuals.

Dataset Information

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

Publications

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

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