Trial reportThe Journal of clinical investigation2015
TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization.
Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 147 citations in OpenAlex.
- A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus.International journal of molecular sciences · 2020Pooled it
- The Human Immune Response to Respiratory Syncytial Virus Infection.Clinical microbiology reviews · 2017Pooled it
- p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus.The Journal of clinical investigation · 2019Trial
- Biomarkers and Risk Factors Associated with Apnea in Hospitalized Infants with Acute Respiratory Infection.Viruses · 2026Article
- Respiratory syncytial virus - from discovery to vaccines.Journal of medical microbiology · 2026Review
- Explainable AI multiomics analysis reveals shared and divergent host responses in COVID-19 and influenza.NPJ digital medicine · 2026Article
- When defense backfires: inflammatory determinants of RSV-induced disease severity.Future virology · 2026Article
- NOD2 (Nucleotide-Binding Oligomerization Domain-Containing Protein 2)-Mediated Modulation of the Immune Response Induced by BCG (Bacillus Calmette-Guérin) Bacilli.Pathogens (Basel, Switzerland) · 2025Article
- Systemic IL-10 and IFN-γ Levels in Respiratory Syncytial Virus- and Rhinovirus-Infected Bulgarian Children with Acute Bronchiolitis and Their Impact on Clinical Manifestation.Pathogens (Basel, Switzerland) · 2025Article
- Exposure to bacterial PAMPs before RSV infection exacerbates innate inflammation and disease via IL-1α and TNF-α.Mucosal immunology · 2024Article
- LPS binding protein and activation signatures are upregulated during asthma exacerbations in children.Respiratory research · 2023Article
- Article
- Association between prenatal and neonatal risk factors and development of bronchiolitis in early life.Asia Pacific allergy · 2023Article
- Host-Pathogen Interactions Influencing Zoonotic Spillover Potential and Transmission in Humans.Viruses · 2023Review
- Infection with soil-transmitted helminths and their impact on coinfections.Frontiers in parasitology · 2023Review
- Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient.The Journal of infectious diseases · 2022Article
- CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns.Nature communications · 2022Article
- Receptors for Respiratory Syncytial Virus Infection and Host Factors Regulating the Life Cycle of Respiratory Syncytial Virus.Frontiers in cellular and infection microbiology · 2022Review
- Editorial: Translational research in pediatric respiratory diseases: From bench to bedside.Frontiers in pediatrics · 2022Article
- Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life.Frontiers in immunology · 2022Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
43 authors at 7 institutions in 2 countries.
Funding
Abstract
While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention.
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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.