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Dynamic optimization reveals alveolar epithelial cells as key mediators of host defense in invasive aspergillosis

Jan Ewald1,2, Flora Rivieccio3,4, Lukáš Radosa3

  • 1Department of Bioinformatics, Friedrich Schiller University Jena, Jena, Germany.

Plos Computational Biology
|December 13, 2021
PubMed

Insights

This study models the race between the immune system and Aspergillus fumigatus fungal growth. Faster germination is a key fungal virulence trait, while epithelial cells aid host defense against invasive aspergillosis.

Area of Science:

  • Mycology
  • Immunology
  • Mathematical Biology

Background:

  • Aspergillus fumigatus is a common human fungal pathogen.
  • Invasive aspergillosis, caused by A. fumigatus, has high mortality rates, especially in immunocompromised individuals.
  • Fungal infection outcome depends on the balance between host immunity and pathogen growth.

Purpose of the Study:

  • To model the dynamics of immune cell recruitment and depletion during A. fumigatus infection.
  • To identify key host and pathogen factors influencing invasive aspergillosis outcomes.
  • To provide insights for improved treatment strategies.

Main Methods:

  • Dynamic optimization modeling was employed to simulate immune responses.
  • In silico predictions were validated through in vitro experiments using cell lines and primary lung cells.
  • Germination speed and epithelial cell roles were specifically investigated.

Main Results:

  • Germination speed was identified as a critical fungal virulence trait, confirmed in vitro.
  • Epithelial cells were found to be important for fungal clearance and cytokine release.
  • Neutrophils are crucial for combating invasive aspergillosis, while macrophage roles require further investigation.

Conclusions:

  • Mathematical modeling offers valuable insights into host-pathogen dynamics in invasive aspergillosis.
  • Targeting fungal germination speed and understanding epithelial cell contributions could improve treatments.
  • Further research is needed to elucidate the precise role of macrophages in A. fumigatus infections.

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