Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli
The healthy state of an organism is constantly threatened by external cues. Due to the daily inhalation of hundreds of particles and pathogens, the immune system needs to constantly accomplish the task of pathogen clearance in order to maintain this healthy state. However, infection dynamics are hig...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.01951/full |
| _version_ | 1811223807641255936 |
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| author | Marco Blickensdorf Marco Blickensdorf Sandra Timme Marc Thilo Figge Marc Thilo Figge |
| author_facet | Marco Blickensdorf Marco Blickensdorf Sandra Timme Marc Thilo Figge Marc Thilo Figge |
| author_sort | Marco Blickensdorf |
| collection | DOAJ |
| description | The healthy state of an organism is constantly threatened by external cues. Due to the daily inhalation of hundreds of particles and pathogens, the immune system needs to constantly accomplish the task of pathogen clearance in order to maintain this healthy state. However, infection dynamics are highly influenced by the peculiar anatomy of the human lung. Lung alveoli that are packed in alveolar sacs are interconnected by so called Pores of Kohn. Mainly due to the lack of in vivo methods, the role of Pores of Kohn in the mammalian lung is still under debate and partly contradicting hypotheses remain to be investigated. Although it was shown by electron microscopy that Pores of Kohn may serve as passageways for immune cells, their impact on the infection dynamics in the lung is still unknown under in vivo conditions. In the present study, we apply a hybrid agent-based infection model to quantitatively compare three different scenarios and discuss the importance of Pores of Kohn during infections of Aspergillus fumigatus. A. fumigatus is an airborne opportunistic fungus with rising incidences causing severe infections in immunocompromised patients that are associated with high mortality rates. Our hybrid agent-based model incorporates immune cell dynamics of alveolar macrophages – the resident phagocytes in the lung – as well as molecular dynamics of diffusing chemokines that attract alveolar macrophages to the site of infection. Consequently, this model allows a quantitative comparison of three different scenarios and to study the importance of Pores of Kohn. This enables us to demonstrate how passaging of alveolar macrophages and chemokine diffusion affect A. fumigatus infection dynamics. We show that Pores of Kohn alter important infection clearance mechanisms, such as the spatial distribution of macrophages and the effect of chemokine signaling. However, despite these differences, a lack of passageways for alveolar macrophages does impede infection clearance only to a minor extend. Furthermore, we quantify the importance of recruited macrophages in comparison to resident macrophages. |
| first_indexed | 2024-04-12T08:39:27Z |
| format | Article |
| id | doaj.art-5ecb1e7222a1438f8bbc4bcacc1b3053 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T08:39:27Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5ecb1e7222a1438f8bbc4bcacc1b30532022-12-22T03:39:56ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-08-011110.3389/fmicb.2020.01951563788Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human AlveoliMarco Blickensdorf0Marco Blickensdorf1Sandra Timme2Marc Thilo Figge3Marc Thilo Figge4Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, GermanyFaculty of Biological Sciences, Institute of Microbiology, Friedrich Schiller University Jena, Jena, GermanyResearch Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, GermanyResearch Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, GermanyFaculty of Biological Sciences, Institute of Microbiology, Friedrich Schiller University Jena, Jena, GermanyThe healthy state of an organism is constantly threatened by external cues. Due to the daily inhalation of hundreds of particles and pathogens, the immune system needs to constantly accomplish the task of pathogen clearance in order to maintain this healthy state. However, infection dynamics are highly influenced by the peculiar anatomy of the human lung. Lung alveoli that are packed in alveolar sacs are interconnected by so called Pores of Kohn. Mainly due to the lack of in vivo methods, the role of Pores of Kohn in the mammalian lung is still under debate and partly contradicting hypotheses remain to be investigated. Although it was shown by electron microscopy that Pores of Kohn may serve as passageways for immune cells, their impact on the infection dynamics in the lung is still unknown under in vivo conditions. In the present study, we apply a hybrid agent-based infection model to quantitatively compare three different scenarios and discuss the importance of Pores of Kohn during infections of Aspergillus fumigatus. A. fumigatus is an airborne opportunistic fungus with rising incidences causing severe infections in immunocompromised patients that are associated with high mortality rates. Our hybrid agent-based model incorporates immune cell dynamics of alveolar macrophages – the resident phagocytes in the lung – as well as molecular dynamics of diffusing chemokines that attract alveolar macrophages to the site of infection. Consequently, this model allows a quantitative comparison of three different scenarios and to study the importance of Pores of Kohn. This enables us to demonstrate how passaging of alveolar macrophages and chemokine diffusion affect A. fumigatus infection dynamics. We show that Pores of Kohn alter important infection clearance mechanisms, such as the spatial distribution of macrophages and the effect of chemokine signaling. However, despite these differences, a lack of passageways for alveolar macrophages does impede infection clearance only to a minor extend. Furthermore, we quantify the importance of recruited macrophages in comparison to resident macrophages.https://www.frontiersin.org/article/10.3389/fmicb.2020.01951/fullvirtual infection modelingAspergillus fumigatus lung infectionPores of Kohnhuman modelhybrid agent-based computer simulations |
| spellingShingle | Marco Blickensdorf Marco Blickensdorf Sandra Timme Marc Thilo Figge Marc Thilo Figge Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli Frontiers in Microbiology virtual infection modeling Aspergillus fumigatus lung infection Pores of Kohn human model hybrid agent-based computer simulations |
| title | Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli |
| title_full | Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli |
| title_fullStr | Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli |
| title_full_unstemmed | Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli |
| title_short | Hybrid Agent-Based Modeling of Aspergillus fumigatus Infection to Quantitatively Investigate the Role of Pores of Kohn in Human Alveoli |
| title_sort | hybrid agent based modeling of aspergillus fumigatus infection to quantitatively investigate the role of pores of kohn in human alveoli |
| topic | virtual infection modeling Aspergillus fumigatus lung infection Pores of Kohn human model hybrid agent-based computer simulations |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.01951/full |
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