New mechanism discovered in the immune defence in the respiratory tract against common ‘hospital germs’

29 January 2025

Tuft cells, which are found on the mucous membranes of the respiratory tract, among other places, are still only incompletely researched. A team led by Gabriela Krasteva-Christ, Professor of Anatomy and Cell Biology at Saarland University, has now discovered how brush cells react to Pseudomonas aeruginosa, a common ‘hospital germ’, and stimulate the immune response. The study has now been published in the renowned scientific journal ‘Nature Communications’.

At first it's just a little scratchy in the throat, at some point the scratchiness turns into a coughing fit that can no longer be suppressed, and then it really starts. The cough becomes more severe, followed by fever, chills and other symptoms. A bacterial infection of the respiratory tract can also quickly develop into pneumonia. Germs such as Pseudomonas aeruginosa trigger such infections, which particularly affect people with pre-existing conditions such as cystic fibrosis or COPD (chronic obstructive pulmonary disease) or whose immune system is weakened due to treatment in hospital. The bacterium is therefore considered one of the most widespread ‘hospital germs’.

However, the body is not defenceless against these invaders. It uses a whole arsenal of weapons or, to put it more scientifically, the ‘immune response’ to tackle the attackers. The so-called brush cells, which are found in the mucous membranes of the respiratory tract, play a special role here. If they become active, an immune response follows. However, for a long time nobody knew exactly what happens. Gabriela Krasteva-Christ is one of the reasons why more is now gradually becoming known about exactly what the brush cells do. The Professor of Anatomy and Cell Biology at Saarland University has been studying these cells for almost two decades.

In a recently published study, Dr Monika Hollenhorst, Dr Mohamed Elhawy and doctoral student Noran Abdel-Wadood from her team have discovered how brush cells in the airways trigger the immune response, or more precisely, the specific or adaptive immune response. ‘Until now, we only knew that brush cells release acetylcholine, a messenger substance that triggers the transmission of stimuli to nerve cells. If the brush cells register an intruder, the acetylcholine ensures that the central nervous system is informed: We cough,’ explains Gabriela Krasteva-Christ. This is followed by what is known as a non-specific immune response. ‘Immune cells from the environment, such as neutrophil granulocytes, are attracted to the site, which attack the intruder very effectively, but non-specifically and not in a targeted manner,’ she explains.

So far, so familiar. ‘This is followed somewhat later by a specific immune response that attacks a germ such as Pseudomonas aeruginosa much more precisely. What role the brush cells play in this has been a mystery until now, however, and it is precisely this mystery that we have now solved,’ explains Dr Mohamed Elhawy. The scientists were the first working group in the world to analyse a native brush cell electrophysiologically using the so-called patch-clamp technique. The team was able to precisely measure how the electrical voltage and the ion current through the cell membrane change. These changes open or close certain channels in the cell membrane in order to release or retain messenger substances.

They have made an observation that does not focus on acetylcholine (ACh), but on another substance that plays an essential role in our body: Adenosine triphosphate, or ATP for short. This usually serves as the body's ‘battery’; the energy that we obtain from food is stored in ATP and made available to the cells.

‘We were able to observe that the brush cells release just enough ATP to trigger the non-specific immune response, the ‘rapid response force’, if you like. In addition, the precisely measured ATP stimulates the activation of dendritic cells, which in turn are essential for the initiation of a specific immune response,’ explains Noran Abdel-Wadood. Dendritic cells are highly specialised cells of the immune system. They virtually ‘bite off’ parts of the pathogen and take it to the lymph nodes, where they use these pathogen-typical parts to train other immune cells on precisely this intruder, so that the body can then fight the pathogenic germ very effectively.

Once this immune response has been initiated, the brush cells stop releasing ATP again. ‘So the reaction doesn't overshoot, but is completely regulated and targeted,’ concludes Monika Hollenhorst. ‘Localised inflammation is therefore limited in time and also terminated.’

This important finding can help to better treat dangerous pneumonia, for example by searching for substances that activate the channel called Trpm5, which stimulates the opening of another channel, Panx1, through which ATP leaves the brush cell. ‘If a drug can specifically regulate ATP and ACh output, it may also be possible to contain dangerous pneumonia,’ explains Gabriela Krasteva-Christ. However, it will be a long time before that happens and many studies will have to follow.

However, Gabriela Krasteva-Christ's team has now laid the foundation for a new way of tackling dangerous pathogens such as Pseudomonas aeruginosa with their new findings on how brush cells work.

Original publication:
Abdel Wadood, N., Hollenhorst, M.I., Elhawy, M.I. et al. Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia. Nat Commun 16, 584 (2025). https://doi.org/10.1038/s41467-025-55936-5