ArticleThe EMBO journal2022
TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS-CoV-2 infection.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 98 citations in OpenAlex.
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- Pediatric viral myocarditis: mechanisms, experimental models, and research gaps.Pediatric research · 2026Review
- Interplay between flaviviruses and the interferon response: mechanisms of immune evasion and therapeutic implications.Frontiers in pharmacology · 2026Review
- Respiratory epithelial cells as central mediators of immune crosstalk in SARS-CoV-2 infection.Frontiers in immunology · 2026Review
- Article
- Deleterious variants in the autophagy-related gene RB1CC1/FIP200 impair immunity to SARS-CoV-2.Nature communications · 2025Article
- Differential response of human plasmacytoid pre-dendritic cells to SARS-CoV-2 variants.iScience · 2025Article
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- Deciphering TLR and JAK/STAT pathways: genetic variants and targeted therapies in COVID-19.Molecular biology reports · 2025Review
- Immunomodulatory Effects of PulmonaromPharmaceuticals (Basel, Switzerland) · 2025Article
- Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.Journal of virology · 2025Article
- Interferon and TLR genes, but not endogenous bornavirus-like elements, limit BoDV1 replication after intracerebral infection.PLoS pathogens · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Interferon Regulatory Factor 3 Exacerbates the Severity of COVID-19 in Mice.Critical care explorations · 2025Article
- SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner.NPJ vaccines · 2025Article
- 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
- Soluble SARS-CoV-2 Spike glycoprotein: considering some potential pathogenic effects.Frontiers in immunology · 2025Review
- Comparative single-cell immune responses in peripheral blood and lymph node of immunized SARS-CoV-2 challenged infant rhesus macaques.Frontiers in immunology · 2025Article
- Characterization of TLR9 responsiveness in cell subsets derived fromFrontiers in immunology · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the molecular pathways driving the acute antiviral and inflammatory response to SARS-CoV-2 infection is critical for developing treatments for severe COVID-19. Here, we find decreasing number of circulating plasmacytoid dendritic cells (pDCs) in COVID-19 patients early after symptom onset, correlating with disease severity. pDC depletion is transient and coincides with decreased expression of antiviral type I IFNα and of systemic inflammatory cytokines CXCL10 and IL-6. Using an in vitro stem cell-based human pDC model, we further demonstrate that pDCs, while not supporting SARS-CoV-2 replication, directly sense the virus and in response produce multiple antiviral (interferons: IFNα and IFNλ1) and inflammatory (IL-6, IL-8, CXCL10) cytokines that protect epithelial cells from de novo SARS-CoV-2 infection. Via targeted deletion of virus-recognition innate immune pathways, we identify TLR7-MyD88 signaling as crucial for production of antiviral interferons (IFNs), whereas Toll-like receptor (TLR)2 is responsible for the inflammatory IL-6 response. We further show that SARS-CoV-2 engages the receptor neuropilin-1 on pDCs to selectively mitigate the antiviral interferon response, but not the IL-6 response, suggesting neuropilin-1 as potential therapeutic target for stimulation of TLR7-mediated antiviral protection.
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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.