Deciphering the Counterplay of Aspergillus fumigatus Infection and Host Inflammation by Evolutionary Games on Graphs.
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.
Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, Germany.
Johannes
J
Pollmächer
Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, Germany.
Sandra
S
Timme
Department of Bioinformatics, Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, Germany.
Stefan
S
Schuster
Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, Germany.|Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
Axel A
AA
Brakhage
Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, Germany.|Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
Peter F
PF
Zipfel
Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.|Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, Germany.
Marc Thilo
MT
Figge
D001232:Aspergillus fumigatus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000382:microbiology; D055732:Pulmonary Aspergillosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D013172:Spores, Fungal / Q000502:physiology