ArticleDisease models & mechanisms2015
Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- A 3D Organotypic Human Bronchial Model Reveals Persistent Infection and Modulated Inflammatory Response when Exposed toTropical medicine and infectious disease · 2026Article
- Alpha-toxin-elicited CXmBio · 2025Article
- Histopathological changes and inflammatory and cell death pathways in the lungs of Balb/c mice with pneumonia induced by different concentrations ofAnatomy & cell biology · 2025Article
- The Susceptibility Profiles of Human Peripheral Blood Cells toMicroorganisms · 2025Review
- Applications and research trends in organoid based infectious disease models.Scientific reports · 2025Review
- Molecular characterization of a novel putative pathogen,Microbiology spectrum · 2024Article
- In vitro high-content tissue models to address precision medicine challenges.Molecular aspects of medicine · 2023Review
- Identification of two neutralizing human single-chain variable fragment antibodies targetingIranian journal of basic medical sciences · 2022Article
- Neutralization of the Staphylococcus aureus Panton-Valentine leukocidin by African and Caucasian sera.BMC microbiology · 2022Article
- Bioactive lipid screening during respiratory tract infections with bacterial and viral pathogens in mice.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Group B Streptococcal Hemolytic Pigment Impairs Platelet Function in a Two-Step Process.Cells · 2022Article
- Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells.Journal of innate immunity · 2022Article
- Review
- Human Organotypic Models for Anti-infective Research.Current topics in microbiology and immunology · 2021Article
- Review
- Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation and development of pneumococcal disease.EMBO molecular medicine · 2020Article
- Impact of Bacterial Toxins in the Lungs.Toxins · 2020Review
- 16HBE Cell Lipid Mediator Responses to Mono and Co-Infections with Respiratory Pathogens.Metabolites · 2020Article
- Atypical Presentation of Methicillin-SusceptiblePathogens (Basel, Switzerland) · 2020Article
- C-Type Lectin Receptors in Host Defense Against Bacterial Pathogens.Frontiers in cellular and infection microbiology · 2020Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The results reveal that the combination and levels of α-toxin and PVL correlate with tissue pathology and clinical outcome associated with pneumonia.
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