A Dynamical Model Examining the Effects of NFkB and HIF1 Pathways in Asergillus fumigatus Infected Airway Epithelial Cells
The ubiquitous fungus, Aspergillus fumigatus, is responsible for an increasing number of deaths each year from airway complications and diseases. In immunocompromised persons, A. fumigatus acts as an opportunistic pathogen, causing potentially fatal infections in the respiratory tract with symptoms including necrosis of the endothelial tissue and extensive inflammation. Evidence is growing indicating that bronchial epithelial cells not only provide a physical barrier of defense to pathogens such as A. fumigatus, but also actively participate in the immune response through a variety of pathways. We present a discrete mathematical model in the form of a polynomial dynamical system representing a snapshot of the transcriptional response of the host to fungal infection, based on RNA-seq data and published literature. This network links A. fumigatus infection to iron import in epithelial cells via a range of fungal recognition and immune response pathways. Iron is an essential nutrient for both humans and fungi, and by examining iron regulation in epithelial cells under stress due to fungal interaction, it is possible to better understand the dynamics of the host and thus identify future targets for research into treatments for invasive pulmonary aspergillosis and other Aspergillus-related diseases. Our model, along with experimental data, indicates that transferrin receptor (TFRC), an important iron-transporter, experiences attenuation during fungal infection and augmentation when hypoxic conditions are present.