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Updated: Feb 26, 2026
Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Modelling the host-pathogen interactions of macrophages and Candida albicans using Game Theory and dynamic
Sybille Dühring1, Jan Ewald2, Sebastian Germerodt2
1Department of Bioinformatics, Friedrich-Schiller-University Jena, Jena, Germany sybille.duehring@uni-jena.de.
Abstract:
The release of fungal cells following macrophage phagocytosis, called non-lytic expulsion, is reported for several fungal pathogens. On one hand, non-lytic expulsion may benefit the fungus in escaping the microbicidal environment of the phagosome. On the other hand, the macrophage could profit in terms of avoiding its own lysis and being able to undergo proliferation. To analyse the causes of non-lytic expulsion and the relevance of macrophage proliferation in the macrophage-Candida albicans interaction, we employ Evolutionary Game Theory and dynamic optimization in a sequential manner. We establish a game-theoretical model describing the different strategies of the two players after phagocytosis. Depending on the parameter values, we find four different Nash equilibria and determine the influence of the systems state of the host upon the game. As our Nash equilibria are a direct consequence of the model parameterization, we can depict several biological scenarios. A parameter region, where the host response is robust against the fungal infection, is determined. We further apply dynamic optimization to analyse whether macrophage mitosis is relevant in the host-pathogen interaction of macrophages and C. albicans For this, we study the population dynamics of the macrophage-C. albicans interactions and the corresponding optimal controls for the macrophages, indicating the best macrophage strategy of switching from proliferation to attacking fungal cells.
Insights
Fungal non-lytic expulsion from macrophages benefits pathogens by aiding escape. Macrophage proliferation can be a beneficial host defense strategy against Candida albicans infection.
Area of Science:
- * Immunology
- * Evolutionary Biology
- * Computational Biology
Background:
- * Non-lytic expulsion is a mechanism where fungal cells are released from macrophages after phagocytosis.
- * This process presents potential benefits for both the fungus (evasion) and the host macrophage (survival and proliferation).
- * Understanding the dynamics of this interaction is crucial for host defense strategies against fungal pathogens like *Candida albicans*.
Purpose of the Study:
- * To analyze the causes and implications of non-lytic expulsion in the macrophage-*Candida albicans* interaction.
- * To investigate the relevance of macrophage proliferation as a host defense mechanism.
- * To model the strategic interactions between macrophages and *Candida albicans* using game theory.
Main Methods:
- * Application of Evolutionary Game Theory to model host-pathogen strategies post-phagocytosis.
- * Utilization of dynamic optimization to analyze macrophage population dynamics and optimal control strategies.
- * Development of a game-theoretical model with sequential decision-making.
Main Results:
- * Identification of four distinct Nash equilibria based on model parameterization, illustrating various biological scenarios.
- * Determination of a parameter region indicating a robust host immune response against fungal infection.
- * Analysis revealing that macrophage mitosis (proliferation) plays a relevant role in the host-pathogen interaction.
Conclusions:
- * The study provides insights into the complex interplay between fungal non-lytic expulsion and macrophage proliferation.
- * Evolutionary game theory and dynamic optimization are valuable tools for dissecting host-pathogen interactions.
- * Identifying optimal macrophage strategies, such as balancing proliferation and direct attack, is key to effective fungal infection control.
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