ArticlePloS one2014
Agent-based model of human alveoli predicts chemotactic signaling by epithelial cells during early Aspergillus fumigatus infection.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Literature Review of Agents Applied in Healthcare.Journal of medical systems · 2016Pooled it
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- Spatiotemporal modeling quantifies cellular contributions to uptake of Aspergillus fumigatus in the human lung.Communications biology · 2024Article
- Epithelial uptake leads to fungal killingiScience · 2024Article
- The transcriptomic signature of respiratory sensitizers using an alveolar model.Cell biology and toxicology · 2024Article
- An In Vitro Alveolar Model Allows for the Rapid Assessment of Particles for Respiratory Sensitization Potential.International journal of molecular sciences · 2023Article
- Surrogate infection model predicts optimal alveolar macrophage number for clearance of Aspergillus fumigatus infections.NPJ systems biology and applications · 2023Article
- An Agent-Based Model of Radiation-Induced Lung Fibrosis.International journal of molecular sciences · 2022Article
- Multi-scale mechanistic modelling of the host defence in invasive aspergillosis reveals leucocyte activation and iron acquisition as drivers of infection outcome.Journal of the Royal Society, Interface · 2022Article
- Novel Insights intoJournal of fungi (Basel, Switzerland) · 2022Review
- Ex vivo immune profiling in patient blood enables quantification of innate immune effector functions.Scientific reports · 2021Article
- Characterisation ofJournal of fungi (Basel, Switzerland) · 2021Article
- Trends in mathematical modeling of host-pathogen interactions.Cellular and molecular life sciences : CMLS · 2020Review
- Hybrid Agent-Based Modeling ofFrontiers in microbiology · 2020Article
- A biomathematical model of immune response and barrier function in mice with pneumococcal lung infection.PloS one · 2020Article
- On the efficiency of chemotactic pursuit - Comparing blind search with temporal and spatial gradient sensing.Scientific reports · 2019Article
- Comparative Assessment of Aspergillosis by Virtual Infection Modeling in Murine and Human Lung.Frontiers in immunology · 2019Article
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2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Aspergillus fumigatus is one of the most important human fungal pathogens, causing life-threatening diseases. Since humans inhale hundreds to thousands of fungal conidia every day, the lower respiratory tract is the primary site of infection. Current interaction networks of the innate immune response attribute fungal recognition and detection to alveolar macrophages, which are thought to be the first cells to get in contact with the fungus. At present, these networks are derived from in vitro or in situ assays, as the peculiar physiology of the human lung makes in vivo experiments, including imaging on the cell-level, hard to realize. We implemented a spatio-temporal agent-based model of a human alveolus in order to perform in silico experiments of a virtual infection scenario, for an alveolus infected with A. fumigatus under physiological conditions. The virtual analog captures the three-dimensional alveolar morphology consisting of the two major alveolar epithelial cell types and the pores of Kohn as well as the dynamic process of respiration. To the best of our knowledge this is the first agent-based model of a dynamic human alveolus in the presence of respiration. A key readout of our simulations is the first-passage-time of alveolar macrophages, which is the period of time that elapses until the first physical macrophage-conidium contact is established. We tested for random and chemotactic migration modes of alveolar macrophages and varied their corresponding parameter sets. The resulting first-passage-time distributions imply that randomly migrating macrophages fail to find the conidium before the start of germination, whereas guidance by chemotactic signals derived from the alveolar epithelial cell associated with the fungus enables a secure and successful discovery of the pathogen in time.
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