ArticleHeliyon2023
SARS-CoV-2 activates the TLR4/MyD88 pathway in human macrophages: A possible correlation with strong pro-inflammatory responses in severe COVID-19.
Article in Heliyon, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Let-7a-5p/SHIP-1 Axis Drives SARS-CoV-2 Spike-1-Induced Microglial Pyroptosis.International journal of molecular sciences · 2026Article
- Computational structural dynamics and immunoinformatic analysis of EIEC IpaHMolecular diversity · 2026Article
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Alterations in the Placenta Following Vaccination and Infection with SARS-CoV-2 During Pregnancy.International journal of molecular sciences · 2026Article
- Mesenchymal Stromal Cells Respond to SARS-CoV-2 Peptides and Exhibit Altered T-Cell Regulatory Capacity.Cells · 2026Article
- The emerging role of TLR7-mediated signaling in respiratory viral infections and autoimmune diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Metatranscriptomic insights into host-microbiome interactions underlying asymptomatic COVID-19 cases.Scientific reports · 2026Article
- Pulmonary fibrosis in post-COVID-19: epithelial-mesenchymal transition as a key mechanism and target for therapy.Inflammopharmacology · 2026Review
- The Post-COVID syndrome caused by excessive inflammation: pathogenesis, potential targets and therapeutic agents.Frontiers in pharmacology · 2026Review
- MYD88 regulates the intercellular crosstalk landscape in MASH liver against metaflammation and metabolic disorder.Acta pharmaceutica Sinica. B · 2025Article
- Potential applications of components of aged garlic extract in mitigating pro-inflammatory gene expression linked to human diseases (Review).Experimental and therapeutic medicine · 2025Review
- Basic implications on three pathways associated with SARS-CoV-2.Biomedical journal · 2025Review
- Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene.Experimental and therapeutic medicine · 2025Article
- SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner.NPJ vaccines · 2025Article
- Patients Hospitalized with COVID-19 Demonstrate Distinct Plasma Cytokine and Chemokine Concentrations in vivo and TLR-Mediated Cytokine and Chemokine Production in Whole Blood in vitro.Journal of innate immunity · 2025Article
- SARS-CoV-2 viral proteins trigger pain via TLR2/4-MyD88 pathway.Frontiers in molecular neuroscience · 2025Article
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- Cyclophilin-CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8.Frontiers in immunology · 2025Article
- The immune receptors TLR4 and SLAMF1 regulate TNF release by human metapneumovirus in human macrophages.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 5 countries.
Funding
Abstract
Background: Toll-like receptors (TLRs) play a pivotal role in the immunologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Exaggerated inflammatory response of innate immune cells, however, may drive morbidity and death in Coronavirus disease 19 (COVID-19). Objective: We investigated the engagement of SARS-CoV-2 with TLR4 in order to better understand how to tackle hyperinflammation in COVID-19. Methods: We combined RNA-sequencing data of human lung tissue and of bronchoalveolar lavage fluid cells derived from COVID-19 patients with functional studies in human macrophages using SARS-CoV-2 spike proteins and viable SARS-CoV-2. Pharmacological inhibitors as well as gene editing with CRISPR/Cas9 were used to delineate the signalling pathways involved. Results: We found TLR4 to be the most abundantly upregulated TLR in human lung tissue irrespective of the underlying pathology. Accordingly, bronchoalveolar lavage fluid cells from patients with severe COVID-19 showed an NF-κB-pathway dominated immune response, whereas they were mostly defined by type I interferon signalling in moderate COVID-19. Mechanistically, we found the Spike ectodomain, but not receptor binding domain monomer to induce TLR4-dependent inflammation in human macrophages. By using pharmacological inhibitors as well as CRISPR/Cas9 deleted macrophages, we identify SARS-CoV-2 to engage canonical TLR4-MyD88 signalling. Importantly, we demonstrate that TLR4 blockage prevents exaggerated inflammatory responses in human macrophages infected with different SARS-CoV-2 variants, including immune escape variants B.1.1.7.-E484K and B.1.1.529 (omicron). Conclusion: Our study critically extends the current knowledge on TLR-mediated hyperinflammatory responses to SARS-CoV-2 in human macrophages, paving the way for novel approaches to tackle severe COVID-19. Take-home message: Our study combining human lung transcriptomics with functional studies in human macrophages clearly supports the design and development of TLR4 - directed therapeutics to mitigate hyperinflammation in severe COVID-19.
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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.