Related Experiment Video
Updated: Mar 19, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Deciphering the Counterplay of Aspergillus fumigatus Infection and Host Inflammation by Evolutionary Games on Graphs
Johannes Pollmächer1,2, Sandra Timme1,2, Stefan Schuster3
1Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
Abstract:
Microbial invaders are ubiquitously present and pose the constant risk of infections that are opposed by various defence mechanisms of the human immune system. A tight regulation of the immune response ensures clearance of microbial invaders and concomitantly limits host damage that is crucial for host viability. To investigate the counterplay of infection and inflammation, we simulated the invasion of the human-pathogenic fungus Aspergillus fumigatus in lung alveoli by evolutionary games on graphs. The layered structure of the innate immune system is represented by a sequence of games in the virtual model. We show that the inflammatory cascade of the immune response is essential for microbial clearance and that the inflammation level correlates with the infection-dose. At low infection-doses, corresponding to daily inhalation of conidia, the resident alveolar macrophages may be sufficient to clear infections, however, at higher infection-doses their primary task shifts towards recruitment of neutrophils to infection sites.
Insights
This study models fungal infections in the lungs, showing that immune system inflammation is key to clearing Aspergillus fumigatus. Higher infection doses trigger neutrophil recruitment by macrophages.
Area of Science:
- Immunology
- Computational Biology
- Mycology
Background:
- The human immune system constantly defends against microbial invaders like Aspergillus fumigatus.
- Effective regulation of immune responses is vital for clearing pathogens and preventing host tissue damage.
Purpose of the Study:
- To investigate the interplay between infection and inflammation using a computational model.
- To simulate Aspergillus fumigatus invasion in lung alveoli and analyze immune system responses.
Main Methods:
- Utilized evolutionary game theory on graphs to model immune responses.
- Represented the innate immune system's layered structure through a sequence of simulated games.
- Simulated fungal invasion in virtual lung alveoli.
Main Results:
- Demonstrated that the inflammatory cascade is essential for microbial clearance.
- Showed a correlation between the level of inflammation and the infection dose.
- Identified that alveolar macrophages are sufficient for low-dose infections but shift to neutrophil recruitment at higher doses.
Conclusions:
- Immune system inflammation is crucial for combating Aspergillus fumigatus infections.
- The immune response dynamically adapts to infection severity, shifting from macrophage-mediated clearance to neutrophil recruitment as needed.
More Related Videos
15:01Confocal Laser Scanning Microscopy-Based Quantitative Analysis of Aspergillus fumigatus Conidia Distribution in Whole-Mount Optically Cleared Mouse Lung
Published on: September 18, 2021
12:29Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
Related Concept Videos
01:28Fungal Phylum Ascomycota
01:28Fungal Phylum Microsporidia
02:39Gene Flow
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:26Factors Affecting the Risk of Infection
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...