Keeping young lungs healthy. Dr Lindsay Marshall, Aston University
Our new HRT-funded research project, to start in July 2014, aims to
determine whether preventing lung infections in childhood can stop
later, life-threatening infections for people with cystic fibrosis (CF).
CF is the most common, inherited disease in the UK, affecting around
9,000 people. People with CF have a decline in lung function with age
and lung disease is their main cause of death, but we still do not fully
The diagram shows how healthy, non-CF
understand the link between the cause of CF and the lung disease.
In a previous HRT project, we successfully developed a model of CF airways. airways defend themselves from
Antimicrobial
peptides
Our model contains the different layers of cells found naturally in the infection.
produced by the airways cells provide
airways and is made entirely from human cells. Our model is extremely
active defence against inhaled ‘invaders’,
representative of what happens in human airways and is both ethically and mucus is produced by specialised goblet
scientifically an improvement upon current animal models of CF. Previous cells and is moved up the airways to
data from our human CF model has shown that the model CF airways are expel these trapped invaders, whilst the
more susceptible to certain types of bacterial infection and suggests that signalling molecule IL-8 will sound the
alarm to recruit other cells to help.
these bacteria may “disarm” airways defences in order to infect.
Our current project will use our models to examine the role that bacterial infections play in driving CF lung disease.
This series of diagrams shows what we think is happening in the CF airways over time. The genetic defect in people with
CF has many harmful consequences; in the lungs it leads to the production of large quantities of thick, dehydrated
mucus that block the airways. Now, so-called ‘opportunistic bacteria’ can infect the airways. During childhood, the
bacterium Staphylococcus aureus (S. aureus) infects after disarming the airways defences by inactivating the antimicrobial peptides (AMP) made by the airways cells. Once the S. aureus infection has deactivated the AMP, a more
harmful bacterium, Pseudomonas aeruginosa (P. aeruginosa) takes advantage of the reduction in defence and “moves
in” (Adolescence). P. aeruginosa then produces toxins to eradicate the S. aureus, allowing it to be the major infecting
organism for over 90% of adults with CF (Adulthood) and the cause of the, eventually fatal, lung damage.
We can use our human cell models to demonstrate that this approach is a valuable and valid alternative to using animal
models of CF and, indeed, is better than using animals since animals do not have CF, they produce a different defence
than people and animals are infected by different bacteria. With the support of the HRT, therefore, we can use our
relevant, human model to better understand a human disease and provide useful, important, clinically relevant
information to improve future treatment strategies for people with CF- making a difference for people and animals!