ArticlePLoS computational biology2021
Dynamic optimization reveals alveolar epithelial cells as key mediators of host defense in invasive aspergillosis.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Molecular mechanisms drivingFrontiers in molecular biosciences · 2026Review
- Protein kinase A signaling regulates immune evasion by shaving and concealing fungal β-1,3-glucan.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Poloxamer 188 stabilized poly (ε-caprolactone) microspheres of voriconazole for targeting pulmonary aspergillosis.Therapeutic delivery · 2025Article
- Article
- Spatiotemporal modeling quantifies cellular contributions to uptake of Aspergillus fumigatus in the human lung.Communications biology · 2024Article
- Unraveling host-pathogen dynamics in a murine Model of septic peritonitis induced by vancomycin-resistantVirulence · 2024Article
- Epithelial uptake leads to fungal killingiScience · 2024Article
- Rethinking Aspergillosis in the Era of Microbiota and Mycobiota.Mycopathologia · 2024Review
- Tracking the uptake of labelled host-derived extracellular vesicles by the human fungal pathogenmicroLife · 2024Article
- Surrogate infection model predicts optimal alveolar macrophage number for clearance of Aspergillus fumigatus infections.NPJ systems biology and applications · 2023Article
- Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway.Cell host & microbe · 2023Article
- 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
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Authors and funding
6 authors.
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Abstract
Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system and the outgrowth of A. fumigatus conidia, we use dynamic optimization to obtain insight into the recruitment and depletion of alveolar macrophages and neutrophils. Using this model, we obtain key insights into major determinants of infection outcome on host and pathogen side. On the pathogen side, we predict in silico and confirm in vitro that germination speed is an important virulence trait of fungal pathogens due to the vulnerability of conidia against host defense. On the host side, we found that epithelial cells, which have been underappreciated, play a role in fungal clearance and are potent mediators of cytokine release. Both predictions were confirmed by in vitro experiments on established cell lines as well as primary lung cells. Further, our model affirms the importance of neutrophils in invasive aspergillosis and underlines that the role of macrophages remains elusive. We expect that our model will contribute to improvement of treatment protocols by focusing on the critical components of immune response to fungi but also fungal virulence traits.
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