ArticleCommunications biology2024
Deficiency of Tlr7 and Irf7 in mice increases the severity of COVID-19 through the reduced interferon production.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- IRF7 Protects Against Severe Influenza A Infection Independently of TLR7 Recognition in Mice.Viruses · 2026Article
- Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.Cardiovascular diabetology · 2026Review
- IRGM1-IRF7 Axis Controls Macrophage Chemotaxis to Orchestrate Skeletal Muscle Regeneration.Inflammation · 2026Article
- The emerging role of TLR7-mediated signaling in respiratory viral infections and autoimmune diseases.Cellular and molecular life sciences : CMLS · 2026Review
- The role of toll-like receptor 7 signaling in mice infected by severe fever with thrombocytopenia syndrome virus.Scientific reports · 2026Article
- Characterization of subchronic lung and brain consequences caused by mouse-adapted SARS-CoV-2 and influenza A infection of C57BL6 mice.Frontiers in immunology · 2026Article
- TLR7 signaling aggravates lung inflammation associated with increased anti-Scl-70 autoantibody production in murine bleomycin-induced systemic sclerosis.Frontiers in immunology · 2026Article
- Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner.Journal of leukocyte biology · 2025Article
- Ageing and dysregulated lung immune responses in fatal COVID-19.Immunity & ageing : I & A · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Modulation ofFrontiers in immunology · 2025Article
- Role of toll-like receptors in pulmonary immunity: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- Enhanced complement activation and MAC formation accelerates severe COVID-19.Cellular and molecular life sciences : CMLS · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Toll-like receptor 7 (Tlr7) deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. To address these questions, we utilize Tlr7 and Irf7 deficiency mice, single-cell RNA analysis together with bone marrow transplantation approaches. We demonstrate that at the early phase of infection, SARS-CoV-2 causes the upregulation of Tlr7, Irf7, and IFN pathways in the lungs of the infected mice. The deficiency of Tlr7 and Irf7 globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma levels in the circulation. The deficiency of Tlr7 tends to cause the reduced production and nuclear translocation of interferon regulatory factor 7 (IRF7) in the lungs of the infected mice, indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen, Tlr7 or Irf7 deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7 leading to IFN production on the development of innate and adaptive immunity against COVID-19.
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