Scientists have discovered a previously unrecognised way that human airways protect lungs from infection – through the action of cilia, tiny hair-like structures lining the respiratory tract.
These structures are known to beat in a coordinated manner to sweep mucus and trapped particles towards the mouth along the epithelial surface that lines the airway.
However, new research indicates that they also generate fluid motion away from the epithelial surface, potentially enhancing the airway’s protective barrier.
Dynamic barrier
New experiments undertaken by Dr Erika Causa and co-workers in Professor Pietro Cicuta’s group at the University of Cambridge, with mathematical modelling by Dr Debasish Das at the University of Strathclyde, shows that this ciliary motion generates not only lateral but also vertical flow, pushing fluid upward from the airway surface.
This “dynamic barrier” likely helps prevent bacteria, viruses and other harmful particles from reaching the cells that line the airways and causing infection.
The study, published in Proceedings of the National Academy of Sciences (PNAS), may help explain the increased susceptibility to infections in individuals with disorders affecting ciliary function, such as cystic fibrosis or primary ciliary dyskinesia.
In such conditions, impaired ciliary beating is associated with compromised mucus clearance. Ex vivo studies have also shown that when cilia become immobile (a state called ciliostasis), viral replication of pathogens like H3N2 influenza increases significantly.
Similarly, SARS-CoV-2, the virus responsible for COVID-19, targets ciliated airway cells, often leaving their cilia shortened, misshapen or unable to beat properly. This ciliary dysfunction can weaken the airway’s defence and allow viral particles to reach deeper regions of the lung.
New understanding
Dr Das, from the Department of Mathematics and Statistics, said: “Our findings show that cilia don’t just move mucus along the airways; they also push fluid upward, away from the lung lining.
“Coordinated ciliary beating not only maintains respiratory health by clearing mucus but also provides a dynamic barrier against pathogen entry. This new understanding could lead to better treatments for lung conditions in which cilia don’t work properly.”
The Cambridge team tracked fluid movement in real time using a cutting-edge method to 'uncage' tiny fluorescent markers within cultured human airway epithelia. They discovered that coordinated ciliary beating produces both fast horizontal flows and slower vertical flows – a combined effect that had not been directly observed before.
To support the experimental work, Dr Das built detailed computer simulations using slender-body theory. These simulations demonstrated that vertical flows arise only when cilia beat in synchrony or in metachronal waves and were absent when they beat randomly, underscoring the importance of coordination for this additional layer of protection.