Mechanistic basis of the antifungal potency of the airway epithelium

Human beings inhale many thousands of toxic or infectious particles daily, which represent a continuous risk to respiratory health. To remain healthy, our lungs must eliminate these noxious particles and maintain a sterile environment. Airborne spores of the most prominent fungal pathogen of human lungs, Aspergillus fumigatus, are a major component of the air we breathe and initiate more than 3 million chronic and 200,000 invasive diseases annually, worldwide.

In European alone aspergillus-related diseases are likely to exceed 2 million in number per year. Some groups of severely immunocompromised patients, such those undergoing bone marrow transplants have just a 10% survival rate once a fungal infection is contracted. Remarkably, while fungal diseases cause more deaths annually than tuberculosis or malaria, we still lack effective drugs to treat them.

I have previously found that the lung epithelium can grab fungal spores, swallow them up, and kill them and that this process is altered in lung cells from patients having a higher risk of fungal lung disease, such as patients with chronic obstructive pulmonary disease (COPD). Using state-of-the-art technologies to study the interaction of genetically-engineered fluorescent fungal mutant strains and mutant lungs cells, I aim to determine how healthy epithelial cells of the human lung recognise fungal spores and kill them, how this process might influence communication between immune cells in the lung environment, and how this process is altered in cells from patients that have a higher risk of fungal disease.

A detailed understanding of how epithelial cells contribute to clear inhaled A. fumigatus and maintain a healthy lung environment will enable us to design new antifungal therapies, and potentially lead to better ways of preventing dangerous responses to other airborne pathogens and pollutants causing lung diseases.