ArticleThe Journal of experimental medicine2021
A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- IRF7 Protects Against Severe Influenza A Infection Independently of TLR7 Recognition in Mice.Viruses · 2026Article
- A CD54-targeted magneto-responsive nanotheranostic for precision treatment of viral pneumonia via CTSB-mediated PANoptosis inhibition.Journal of nanobiotechnology · 2026Article
- Update on the Efficacy of Vaccination on Host Immunity to Influenza Virus Infection.International archives of allergy and immunology · 2026Review
- TLR7-mediated inflammation drives PD-L1 upregulation and T cell exhaustion during influenza A virus infection.iScience · 2026Article
- Article
- In Silico Prediction of Potential pTLR7/pSTING Dual-Targeting Ligands via Virtual Screening and Molecular Dynamics Simulation.International journal of molecular sciences · 2025Article
- Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections.Nature immunology · 2025Article
- TLR7 deficiency enhances inflammation in the URT but reduces LRT immunity following influenza A infection.Scientific reports · 2025Article
- SAMD9 senses cytosolic double-stranded nucleic acids in epithelial and mesenchymal cells to induce antiviral immunity.Nature communications · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- From defense to offense: Modulating toll-like receptors to combat arbovirus infections.Human vaccines & immunotherapeutics · 2024Review
- TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness.International journal of molecular sciences · 2024Article
- Interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical regulator of inflammatory signalling through toll-like receptors 4 and 7/8 in murine and human lungs.British journal of pharmacology · 2024Article
- Defining the balance between optimal immunity and immunopathology in influenza virus infection.Nature reviews. Immunology · 2024Review
- The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond.Cellular & molecular immunology · 2024Review
- Maternal immune activation with toll-like receptor 7 agonist during mid-gestation alters juvenile and adult developmental milestones and behavior.Journal of neuroendocrinology · 2024Article
- Recent Advances on Small-Molecule Antagonists Targeting TLR7.Molecules (Basel, Switzerland) · 2023Review
- TLR7 promotes chronic airway disease in RSV-infected mice.Frontiers in immunology · 2023Article
- Insights into pandemic respiratory viruses: manipulation of the antiviral interferon response by SARS-CoV-2 and influenza A virus.Current opinion in immunology · 2022Review
- Potential pharmacologic interventions targeting TLR signaling in placental malaria.Trends in parasitology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytokine-mediated immune-cell recruitment and inflammation contribute to protection in respiratory virus infection. However, uncontrolled inflammation and the "cytokine storm" are hallmarks of immunopathology in severe infection. Cytokine storm is a broad term for a phenomenon with diverse characteristics and drivers, depending on host genetics, age, and other factors. Taking advantage of the differential use of virus-sensing systems by different cell types, we test the hypothesis that specifically blocking TLR7-dependent, immune cell-produced cytokines reduces influenza-related immunopathology. In a mouse model of severe influenza characterized by a type I interferon (IFN-I)-driven cytokine storm, TLR7 antagonist treatment leaves epithelial antiviral responses unaltered but acts through pDCs and monocytes to reduce IFN-I and other cytokines in the lung, thus ameliorating inflammation and severity. Moreover, even in the absence of IFN-I signaling, TLR7 antagonism reduces inflammation and mortality driven by monocyte-produced chemoattractants and neutrophil recruitment into the infected lung. Hence, TLR7 antagonism reduces diverse types of cytokine storm in severe influenza.
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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.