ArticlePLoS pathogens2021
Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection.
Article in PLoS pathogens, 2021. 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.
- Sex differences in immune modulation: implications for infection, inflammation, and nutritional supplementation.Biology of sex differences · 2026Review
- Immune Delay, Beyond Immune Evasion, as a Driver of Pathogen Propagation Competence Through Neutrophil Dysregulation, to be Mitigated by Low-Frequency Electromagnetic Fields (LF-EMF).International journal of molecular sciences · 2025Review
- Bridging pDCs and cDCs: The Identity of Transitional Dendritic Cells.Immunological reviews · 2025Review
- Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages.Journal of clinical immunology · 2025Article
- Differential response of human plasmacytoid pre-dendritic cells to SARS-CoV-2 variants.iScience · 2025Article
- New insights into the role of IFN-α/β and TLR7/8/9 in cancer immunotherapy and systemic autoimmunity.Journal for immunotherapy of cancer · 2025Review
- Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains.The Journal of experimental medicine · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Sensing of SARS-CoV-2-infected cells by plasmacytoid dendritic cells is modulated via an interplay between CD54/ICAM-1 and CD11a/LFA-1 αJournal of virology · 2025Article
- Interferon Upregulation Associates with Insulin Resistance in Humans.Current diabetes reviews · 2025Review
- Bovine Lactoferrin Enhances Toll-like Receptor 7 Response in Plasmacytoid Dendritic Cells and Modulates Cellular Immunity.International journal of molecular sciences · 2024Article
- The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond.Cellular & molecular immunology · 2024Review
- Article
- Nucleotide-Binding Oligomerization Domain 1 (NOD1) Agonists Prevent SARS-CoV-2 Infection in Human Lung Epithelial Cells through Harnessing the Innate Immune Response.International journal of molecular sciences · 2024Article
- The role of dendritic cells in respiratory viral infection.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease.Journal of translational medicine · 2024Article
- Identification of an immunological signature of long COVID syndrome.Frontiers in immunology · 2024Article
- Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung.Frontiers in immunology · 2024Article
- A Review on Role of Inflammation in Coronavirus Disease.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Role of innate immunity in SARS-CoV-2 infection.Biosafety and health · 2023Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.