Comparative Assessment of Aspergillosis by Virtual Infection Modeling in Murine and Human Lung

Area of Science:

• Mycology
• Immunology
• Computational Biology

Background:

• * *Aspergillus fumigatus* is an opportunistic fungal pathogen causing severe infections in immunocompromised individuals.
• * Alveolar macrophages are the primary defense against inhaled fungal conidia in the lungs.
• * Current mouse models for *A. fumigatus* infections have limitations due to physiological differences and high infection doses compared to human exposure.

Purpose of the Study:

• * To compare *Aspergillus fumigatus* infection dynamics in mice and humans using virtual modeling.
• * To investigate the influence of lung physiology and infection dose on spatial infection dynamics.
• * To quantitatively assess and compare the efficiency of fungal infection clearance in mice versus humans.

Main Methods:

• * Development and application of a hybrid agent-based model for virtual infection simulation.
• * Incorporation of host-specific lung physiology and varying infection doses into the model.
• * Comparative quantification of spatial infection dynamics and clearance rates in silico.

Main Results:

• * Computer simulations enabled a quantitative comparison of *A. fumigatus* infection clearance in mice and humans.
• * The study elucidated the interplay between alveolar structure and fungal burden.
• * For realistic fungal burdens, infection clearance was found to be more efficient in mice than in humans.

Conclusions:

• * Virtual infection modeling provides a valuable tool for comparing host-pathogen dynamics across species.
• * Mouse models may overestimate clearance efficiency due to physiological and dosage differences.
• * Findings highlight the need for careful consideration of these factors in translating research from mice to human clinical applications.