Plasmacytoid dendritic cells produce type I interferon and reduce viral replication in airway epithelial cells after SARS-CoV-2 infection
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Abstract
Infection with SARS-CoV-2 has caused a pandemic of unprecedented dimensions. SARS-CoV-2 infects airway and lung cells causing viral pneumonia. The importance of type I interferon (IFN) production for the control of SARS-CoV-2 infection is highlighted by the increased severity of COVID-19 in patients with inborn errors of type I IFN response or auto-antibodies against IFN-α. Plasmacytoid dendritic cells (pDCs) are a unique immune cell population specialized in recognizing and controlling viral infections through the production of high concentrations of type I IFN. In this study, we isolated pDCs from healthy donors and showed that pDCs are able to recognize SARS-CoV-2 and rapidly produce large amounts of type I IFN. Sensing of SARS-CoV-2 by pDCs was independent of viral replication since pDCs were also able to recognize UV-inactivated SARS-CoV-2 and produce type I IFN. Transcriptional profiling of SARS-CoV-2 and UV-SARS-CoV-2 stimulated pDCs also showed a rapid type I and III IFN response as well as induction of several chemokines, and the induction of apoptosis in pDCs. Moreover, we modeled SARS-CoV-2 infection in the lung using primary human airway epithelial cells (pHAEs) and showed that co-culture of pDCs with SARS-CoV-2 infected pHAEs induces an antiviral response and upregulation of antigen presentation in pHAE cells. Importantly, the presence of pDCs in the co-culture results in control of SARS-CoV-2 replication in pHAEs. Our study identifies pDCs as one of the key cells that can recognize SARS-CoV-2 infection, produce type I and III IFN and control viral replication in infected cells.
Importance
Type I interferons (IFNs) are a major part of the innate immune defense against viral infections. The importance of type I interferon (IFN) production for the control of SARS-CoV-2 infection is highlighted by the increased severity of COVID-19 in patients with defects in the type I IFN response. Interestingly, many cells are not able to produce type I IFN after being infected with SARS-CoV-2 and cannot control viral infection. In this study we show that plasmacytoid dendritic cells are able to recognize SARS-CoV-2 and produce type I IFN, and that pDCs are able to help control viral infection in SARS-CoV-2 infected airway epithelial cells.
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SciScore for 10.1101/2021.05.12.443948: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Plasmacytoid dendritic cell isolation: Deidentified human blood from healthy individuals was collected with the approval of the Internal Review Board (IRB) of Emory University number IRB00045821. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Permeabilized cell monolayers were incubated with an anti-SARS-CoV-2 spike protein primary antibody (provided by Jens Wrammert, Emory University) conjugated to biotin for 2 hours at room temperature (RT), then washed 3 times. anti-SARS-CoV-2 spike proteinsuggested: NoneExperimental Models: Cell Lines Sen… SciScore for 10.1101/2021.05.12.443948: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Plasmacytoid dendritic cell isolation: Deidentified human blood from healthy individuals was collected with the approval of the Internal Review Board (IRB) of Emory University number IRB00045821. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Permeabilized cell monolayers were incubated with an anti-SARS-CoV-2 spike protein primary antibody (provided by Jens Wrammert, Emory University) conjugated to biotin for 2 hours at room temperature (RT), then washed 3 times. anti-SARS-CoV-2 spike proteinsuggested: NoneExperimental Models: Cell Lines Sentences Resources VeroE6 cells were cultured in complete DMEM medium consisting of 1x DMEM (Corning Cellgro), 10% FBS, 25 mM HEPES Buffer (Corning Cellgro), 2 mM L-glutamine, 1mM sodium pyruvate, 1x Non-essential Amino Acids, and 1x antibiotics. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources Reads were normalized and differentially expressed genes were analyzed using DESeq2 (Bioconductor) DESeq2suggested: (DESeq, RRID:SCR_000154)Bioconductorsuggested: (Bioconductor, RRID:SCR_006442)The raw data of all RNA sequencing will be deposited into the Gene Expression Omnibus (GEO) repository and the accession number will be available following acceptance of this manuscript. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Statistical analysis: Statistical analyses were performed using GraphPad Prism 8 GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)8, ggplot2 R package, and GSEA software. ggplot2suggested: (ggplot2, RRID:SCR_014601)GSEAsuggested: (SeqGSEA, RRID:SCR_005724)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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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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