Observational studyThe Journal of allergy and clinical immunology2020
RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness.
Observational study in The Journal of allergy and clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Computational identification of novel therapeutic candidates for Streptococcus pyogenes and influenza A coinfections through transcriptomic-based drug repositioning.BMC microbiology · 2026Article
- Article
- Antiviral Activity of Marine BacteriumInternational journal of molecular sciences · 2025Article
- Dysfunctional neutrophil type 1 interferon responses in preschool children with recurrent wheezing and IL-4-mediated aeroallergen sensitization.The journal of allergy and clinical immunology. Global · 2024Article
- Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists.Biomaterials · 2023Article
- Association of Asthma With Treatments and Outcomes in Children With Critical Influenza.The journal of allergy and clinical immunology. In practice · 2023Observational
- Pathobiology, Severity, and Risk Stratification of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2023Review
- Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.Frontiers in immunology · 2023Article
- Research progress on the effect of traditional Chinese medicine on the activation of PRRs-mediated NF-κB signaling pathway to inhibit influenza pneumonia.Frontiers in pharmacology · 2023Review
- DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.The Journal of infectious diseases · 2022Article
- Functional immunophenotyping of children with critical status asthmaticus identifies differential gene expression responses in neutrophils exposed to a poly(I:C) stimulus.Scientific reports · 2022Observational
- [Therapeutic Effect of Artesunate on Influenza A Viral Pneumonia].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Article
- Immune Immunomodulation in Coronavirus Disease 2019 (COVID-19): Strategic Considerations for Personalized Therapeutic Intervention.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Immune Function in Critically Ill Septic Children.Pathogens (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
16 authors at 11 institutions in 1 country.
Funding
Abstract
backgroundDecreased TNF-α production in whole blood after ex vivo LPS stimulation indicates suppression of the Toll-like receptor (TLR)4 pathway. This is associated with increased mortality in pediatric influenza critical illness. Whether antiviral immune signaling pathways are also suppressed in these patients is unclear.
objectivesWe sought to evaluate suppression of the TLR4 and the antiviral retinoic acid-inducible gene-I (RIG-I) pathways with clinical outcomes in children with severe influenza infection.
methodsIn this 24-center, prospective, observational cohort study of children with confirmed influenza infection, blood was collected within 72 hours of intensive care unit admission. Ex vivo whole blood stimulations were performed with matched controls using the viral ligand polyinosinic-polycytidylic acid-low-molecular-weight/LyoVec and LPS to evaluate IFN-α and TNF-α production capacities (RIG-I and TLR4 pathways, respectively).
resultsSuppression of either IFN-α or TNF-α production capacity was associated with longer duration of mechanical ventilation and hospitalization, and increased organ dysfunction. Children with suppression of both RIG-I and TLR4 pathways (n = 33 of 103 [32%]) were more likely to have prolonged (≥7 days) multiple-organ dysfunction syndrome (30.3% vs 8.6%; P = .004) or prolonged hypoxemic respiratory failure (39.4% vs 11.4%; P = .001) compared with those with single- or no pathway suppression.
conclusionsSuppression of both RIG-I and TLR4 signaling pathways, essential for respective antiviral and antibacterial responses, is common in previously immunocompetent children with influenza-related critical illness and is associated with bacterial coinfection and adverse outcomes. Prospective testing of both pathways may aid in risk-stratification and in immune monitoring.
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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.