Comparative Assessment of Aspergillosis by Virtual Infection Modeling in Murine and Human Lung
Authored by Marc Thilo Figge, Marco Blickensdorf, Sandra Timme
Date Published: 2019
DOI: 10.3389/fimmu.2019.00142
Sponsors:
German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)
Platforms:
C++
Model Documentation:
Other Narrative
Model Code URLs:
Model code not found
Abstract
Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen that
can cause severe infections in immunocompromised patients. Conidia that
reach the lower respiratory tract are confronted with alveolar
macrophages, which are the resident phagocytic cells, constituting the
first line of defense. If not efficiently removed in time, A. fumigatus
conidia can germinate causing severe infections associated with high
mortality rates. Mice are the most extensively used model organism in
research on A. fumigatus infections. However, in addition to structural
differences in the lung physiology of mice and the human host, applied
infection doses in animal experiments are typically orders of magnitude
larger compared to the daily inhalation doses of humans. The influence
of these factors, which must be taken into account in a quantitative
comparison and knowledge transfer from mice to humans, is difficult to
measure since in vivo live cell imaging of the infection dynamics under
physiological conditions is currently not possible. In the present
study, we compare A. fumigatus infection in mice and humans by virtual
infection modeling using a hybrid agent-based model that accounts for
the respective lung physiology and the impact of a wide range of
infection doses on the spatial infection dynamics. Our computer
simulations enable comparative quantification of A. fumigatus infection
clearance in the two hosts to elucidate (i) the complex interplay
between alveolar morphometry and the fungal burden and (ii) the dynamics
of infection clearance, which for realistic fungal burdens is found to
be more efficiently realized in mice compared to humans.
Tags
systems biology
Mice
Size
Fumigatus
Alveolar macrophages
Mouse
Pathogenesis
Morphometry
Virtual infection modeling
Aspergillus fumigatus lung infection
Mouse
model
Human model
Hybrid agent-based computer simulations
Interalveolar pores
Cell
numbers