Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
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Abstract
Emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 ( n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR + CD68 + CD163 + SIGLEC1 + macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor SARS-CoV-2 while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery.
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SciScore for 10.1101/2021.06.28.450153: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The lung sections were stained for macrophages with anti-CD68 antibody, SIGLEC1 with anti-CD169 antibody, Mac_IFN_1 signature markers with anti-MX1, MX2 and ISG15 antibodies; Mac-TREM2 with anti C1q-FITC conjugated antibody and pDCs with anti-HLA-DR and anti-CD123 antibodies to validate the in-vivo expression of these markers in SARS CoV-2 infected lung tissue (Table S2). anti-CD68suggested: Noneanti-CD169suggested: Noneanti-MX1, MX2suggested: NoneISG15suggested: Noneanti C1q-FITCsuggested: Noneanti-HLA-DRsuggested: (BD Biosciences Cat# 341068, RRID:AB_2264695)anti-CD123suggested: NoneSARS CoV-2 … SciScore for 10.1101/2021.06.28.450153: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The lung sections were stained for macrophages with anti-CD68 antibody, SIGLEC1 with anti-CD169 antibody, Mac_IFN_1 signature markers with anti-MX1, MX2 and ISG15 antibodies; Mac-TREM2 with anti C1q-FITC conjugated antibody and pDCs with anti-HLA-DR and anti-CD123 antibodies to validate the in-vivo expression of these markers in SARS CoV-2 infected lung tissue (Table S2). anti-CD68suggested: Noneanti-CD169suggested: Noneanti-MX1, MX2suggested: NoneISG15suggested: Noneanti C1q-FITCsuggested: Noneanti-HLA-DRsuggested: (BD Biosciences Cat# 341068, RRID:AB_2264695)anti-CD123suggested: NoneSARS CoV-2 nucleocapsid antibody was used to detect SARS CoV-2 and ACE-2 expression was confirmed using human anti-ACE2 antibody. anti-ACE2suggested: NoneSoftware and Algorithms Sentences Resources We aligned resulting fastq files on mmul10 genome (Genebank, https://www.ncbi.nlm.nih.gov/assembly/GCF_003339765.1/), with addition of Ensembl mmul8 mitochondrial genes for GTF file with cellranger count. Ensemblsuggested: (Ensembl, RRID:SCR_002344)Circos Plots: Circos plots depicting possible cell interactions were created using SingleCellSignalR 81. Circossuggested: (Circos, RRID:SCR_011798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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