ArticleScientific reports2017
THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Alcohol and Cannabinoids Differentially Regulate Macrophage Polarization, with Co-Exposure Producing an Antagonistic Immunomodulatory Effect.International journal of molecular sciences · 2026Article
- Non-coding RNA Networks in Infection.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis.Cell communication and signaling : CCS · 2023Article
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- Multi-Level Computational Modeling of Anti-Cancer Dendritic Cell Vaccination Utilized to Select Molecular Targets for Therapy Optimization.Frontiers in cell and developmental biology · 2021Article
- The Role of Age, Neutrophil Infiltration and Antibiotics Timing in the Severity ofInternational journal of molecular sciences · 2020Article
- Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.The European respiratory journal · 2020Review
- Article
- Capturing the Onset of Bacterial Pulmonary Infection in Acini-On-Chips.Advanced biosystems · 2019Article
- Use of precision cut lung slices as a translational model for the study of lung biology.Respiratory research · 2019Review
- Bacterial Adherence and Dwelling Probability: Two Drivers of Early Alveolar Infection byFrontiers in cellular and infection microbiology · 2018Article
- Can Gamification Contribute to Computer Modeling-Driven Biomedical Research?Frontiers in physiology · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune response in the lung has to protect the huge alveolar surface against pathogens while securing the delicate lung structure. Macrophages and alveolar epithelial cells constitute the first line of defense and together orchestrate the initial steps of host defense. In this study, we analysed the influence of macrophages on type II alveolar epithelial cells during Legionella pneumophila-infection by a systems biology approach combining experimental work and mathematical modelling. We found that L. pneumophila-infected THP-1-derived macrophages provoke a pro-inflammatory activation of neighboring lung epithelial cells, but in addition render them hypo-responsive to direct infection with the same pathogen. We generated a kinetic mathematical model of macrophage activation and identified a paracrine mechanism of macrophage-secreted IL-1β inducing a prolonged IRAK-1 degradation in lung epithelial cells. This intercellular crosstalk may help to avoid an overwhelming inflammatory response by preventing excessive local secretion of pro-inflammatory cytokines and thereby negatively regulating the recruitment of immune cells to the site of infection. This suggests an important but ambivalent immunomodulatory role of macrophages in lung infection.
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