In vitro-generated respiratory mucosa: a new tool to study inhalational anthrax

Area of Science:

• Biomedical Engineering
• Infectious Disease Research
• Cell Biology

Background:

• Inhalational anthrax poses a significant threat, necessitating better models to study infection dynamics.
• Understanding the early cellular interactions at the air-blood barrier is crucial for developing effective countermeasures.

Purpose of the Study:

• To create a novel three-dimensional (3-D) human airway tissue model for studying the initiation of inhalational anthrax.
• To investigate the roles and interdependence of epithelial cells and macrophages in the respiratory tract's defense against Bacillus anthracis.

Main Methods:

• Generation of a 3-D airway model using human airway epithelial cells cultured on a collagen/fibronectin gel at an air-liquid interface.
• Co-culture of the epithelial model with human blood-derived monocytes, which differentiated into resident macrophages.
• Evaluation of macrophage phenotype through specific cell surface marker expression.

Main Results:

• The 3-D model successfully replicated the in vivo morphology of airway tissues, including the air-blood barrier.
• Monocytes differentiated into functional resident macrophages within the model.
• The model demonstrated the synergistic role of epithelial cells and macrophages in clearing anthrax spores and protecting against infection.

Conclusions:

• The developed 3-D human airway model is effective for studying inhalational anthrax pathogenesis.
• Epithelial cells and macrophages exhibit interdependence in clearing anthrax spores.
• Airway epithelial cells play a protective role against anthrax infection.