ArticleScience immunology2022
Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 85 citations in OpenAlex.
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- ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy.Nature immunology · 2026Article
- IFNλ4 Gene Variants Are Associated with CD8Biomolecules · 2026Article
- Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Identifying ICAM-1 as a Therapeutic Target for Cytokine Storm in Human Macrophages Through Integrative Bioinformatics Approaches.Molecules (Basel, Switzerland) · 2026Article
- TLR7-mediated inflammation drives PD-L1 upregulation and T cell exhaustion during influenza A virus infection.iScience · 2026Article
- Chromatin-mediated anticipatory control of type I interferon production in plasmacytoid dendritic cells.Immunity · 2026Article
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- CD63Frontiers in cellular and infection microbiology · 2026Article
- Respiratory epithelial cells as central mediators of immune crosstalk in SARS-CoV-2 infection.Frontiers in immunology · 2026Review
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections.Nature immunology · 2025Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Differential response of human plasmacytoid pre-dendritic cells to SARS-CoV-2 variants.iScience · 2025Article
- Single-dose cathepsin L CRISPR nanotherapy mitigates PASC-like lung damage in hamsters.Nano research · 2025Article
- Glutamate utilization fuels rapid production of mitochondrial ROS in dendritic cells and drives systemic inflammation during tularemia.Science advances · 2025Article
- Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains.The Journal of experimental medicine · 2025Article
- Interferon-β treatment reverses the detrimental effect of B-cell depletion therapy on respiratory virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Lung-infiltrating macrophages create a marked inflammatory milieu in a subset of patients with COVID-19 by producing a cytokine storm, which correlates with increased lethality. However, these macrophages are largely not infected by SARS-CoV-2, so the mechanism underlying their activation in the lung is unclear. Type I interferons (IFN-I) contribute to protecting the host against SARS-CoV-2 but may also have some deleterious effect, and the source of IFN-I in the lungs of infected patients is not well defined. Plasmacytoid dendritic cells (pDCs), a key cell type involved in antiviral responses, can produce IFN-I in response to SARS-CoV-2. We observed the infiltration of pDCs in the lungs of SARS-CoV-2-infected patients, which correlated with strong IFN-I signaling in lung macrophages. In patients with severe COVID-19, lung macrophages expressed a robust inflammatory signature, which correlated with persistent IFN-I signaling at the single-cell level. Hence, we observed the uncoupling in the kinetics of the infiltration of pDCs in the lungs and the associated IFN-I signature, with the cytokine storm in macrophages. We observed that pDCs were the dominant IFN-α-producing cells in response to the virus in the blood, whereas macrophages produced IFN-α only when in physical contact with infected epithelial cells. We also showed that IFN-α produced by pDCs, after the sensing of SARS-CoV-2 by TLR7, mediated changes in macrophages at both transcriptional and epigenetic levels, which favored their hyperactivation by environmental stimuli. Together, these data indicate that the priming of macrophages can result from the response by pDCs to SARS-CoV-2, leading to macrophage activation in patients with severe COVID-19.
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