See project title below.

The impact of macrophages on non-typeable haemophilus influenzae biofilms in a primary respiratory epithelial cell co-culture and implications in primary ciliary dyskinesia.

Non-typeable Haemophilus Influenza (NTHi) is an opportunistic respiratory bacterial pathogen. It is found as a commensal organism in the nasopharynx but is also an opportunistic pathogen that can cause infections in the upper and lower respiratory tract. Primary Ciliary Dyskinesia (PCD) is a rare genetic disease that impairs the structure and function of cilia. Cilia are responsible for clearing the airways of pathogens and debris through a co-ordinated beating motion. When this clearance is impaired due to PCD, NTHi is able to colonise further down the airway where it has the capacity to form biofilms and cause infection. Biofilms are an aggregation of bacterial cells encased in an extracellular matrix of protein, polysaccharides, lipids and DNA. Bacteria within biofilms are protected from threats such as the immune system and antibiotics. This increased tolerance to antibiotics and the slime-like extracellular matrix makes biofilms very hard to remove and thus causes chronic colonisation and infection. Combined with the reduced ciliary clearance, biofilm infections in PCD patients are a major source of morbidity.

Previous work has established a co-culture method that allows the investigation of NTHi biofilm formation on primary respiratory epithelial cells. This project aims to include macrophages in this model to investigate the interaction of the immune system with NTHi biofilm formation. Macrophages from PCD patients have been shown to react more strongly to challenge by pathogens and react differently when in the presence of epithelial cells. We hypothesise that these macrophages are incapable of clearing NTHi biofilms formed on PCD epithelium, which as a result causes an enhanced immune response that damages the surrounding tissue. This project brings these three components together to produce a model that cannot only be used to increase our understanding of biofilm infections in PCD patients but can also be adapted to investigate a range of respiratory infections, aiding the wider scientific and medical community.