ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Synergistic interactions of TLR2/6 and TLR9 induce a high level of resistance to lung infection in mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed.
- Review
- cJun-assisted loading of RelA DNA-binding promotes synergistic lung epithelial antimicrobial responses.iScience · 2026Article
- Article
- Co-Delivery of Multiple Toll-Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy.Advanced healthcare materials · 2025Article
- Pharmacogenomic Study of SARS-CoV-2 Treatments: Identifying Polymorphisms Associated with Treatment Response in COVID-19 Patients.Biomedicines · 2025Article
- Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.Antimicrobial agents and chemotherapy · 2024Article
- The RNA receptor RIG-I binding synthetic oligodeoxynucleotide promotes pneumonia survival.JCI insight · 2024Article
- Topical adjunctive treatment with flagellin augments pulmonary neutrophil responses and reduces bacterial dissemination in multidrug-resistantFrontiers in immunology · 2024Article
- Engineering Protein Nanoparticles Functionalized with an ImmunodominantBioconjugate chemistry · 2023Article
- Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation.PLoS pathogens · 2023Article
- Epithelial STAT3: A New Twist in Inducible Antimicrobial Resistance.American journal of respiratory cell and molecular biology · 2023Article
- Redox-Dependent Activation of Lung Epithelial STAT3 Is Required for Inducible Protection against Bacterial Pneumonia.American journal of respiratory cell and molecular biology · 2023Article
- Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial metabolic reprogramming.bioRxiv : the preprint server for biology · 2023Article
- Toll-like receptors 2, 4, and 9 modulate promoting effect of COPD-like airway inflammation on K-ras-driven lung cancer through activation of the MyD88/NF-ĸB pathway in the airway epithelium.Frontiers in immunology · 2023Article
- Context-Dependent Roles for Toll-Like Receptors 2 and 9 in the Pathogenesis of Staphylococcus aureus Osteomyelitis.Infection and immunity · 2022Article
- Minimizing caging effects in murine lung microbiome studies.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Airway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung.Nature communications · 2022Article
- OBIF: an omics-based interaction framework to reveal molecular drivers of synergy.NAR genomics and bioinformatics · 2022Article
- Nontypeable Haemophilus influenzae Infection Impedes Pseudomonas aeruginosa Colonization and Persistence in Mouse Respiratory Tract.Infection and immunity · 2022Article
- A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge WithFrontiers in microbiology · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have focused historically on antibiotic development and vaccine-enhanced adaptive immunity. However, we have reported recently that the lungs' innate defenses can be induced therapeutically by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia. In this study, we tested in mice the hypothesis that TLRs are required for this antimicrobial phenomenon and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88. We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands. Although most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent gram-positive and gram-negative pathogens. Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation. Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability.
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