In this project, a virtual infection with A. fumigatus in human or murine alveolus is simulated. The corresponding model considers a realistic to-scale representation of the alveolus, consisting of a 3⁄4 sphere, with alveolar epithelial cells (AEC) of type 1 and 2 as well as pores of Kohn (PoK). Moreover, the AEC, on which a conidium is located, secretes chemokines that diffuse on the inner surface of the alveolus using a system of partial differential equations (PDE). Alveolar macrophages (AM), that represent the first line of immune cells, are able to sense the chemokine gradient using an intracellular receptor-ligand model based on ordinary differential equations (ODE), which directs their migration towards the conidium. The use of this hybrid spatio-temporal approach to modeling interactions between agents at the cellular level allowed us to perform a large number of simulations to gain a quantitative understanding, address open questions, and contribute to the scientific field.
Realistic to-scale representation of murine (left) and human (right) alveolus, consisting of a 3⁄4 sphere and its components.
Virtual infection scenario with A. fumigatus:
Publications
- Blickensdorf et al. (2020). Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli. Frontiers in Microbiology, 11(Aug), 1–13.
- Blickensdorf et al. (2019). Comparative assessment of aspergillosis by virtual infection modeling in murine and human lung. Frontiers in Immunology, 10(Feb).
- Pollmächer et al. (2015). Deciphering chemokine properties by a hybrid agent-based model of Aspergillus fumigatus infection in human alveoli. Frontiers in Microbiology, 6(May), 1–14.
- Pollmächer et al. (2014). Agent-based model of human alveoli predicts chemotactic signaling by epithelial cells during early Aspergillus fumigatus infection. PLoS ONE, 9(10).
