Understanding How Our Lungs Fight Fungus
By Lauren Amphlett

Airway epithelial cells (AECs) are a key component of the human respiratory system: The first line of defence against airborne pathogens such as Aspergillus fumigatus (Af), AECs play a crucial role in initiating host defence and controlling immune responses and are important in maintaining respiratory health and preventing infections that can lead to conditions such as aspergillosis. Research by the University of Manchester’s Dr Margherita Bertuzzi and her team sought to understand how AECs combat Af and what leads to vulnerabilities in these defences, particularly in individuals with underlying health conditions. 

Previous work by Dr Bertuzzi and her team demonstrated that AECs are effective in stopping the fungus from causing harm when they are functioning well. However, in people who are at higher risk, like those with weakened immune systems or existing lung conditions, if these cells are not working correctly, the fungus can take advantage of this situation.

This new research by Dr Bertuzzi and her team aimed to explore how AECs stop the fungus in healthy people and what goes wrong in people who get sick. The team looked closely at the interaction between the fungus and lung cells from both healthy individuals and those with certain diseases. Using advanced scientific methods, the team was able to observe the interactions between the lung cells and the fungus at a very detailed level.

What They Found 

Experiments showed that the stage of fungal growth was important and a surface carbohydrate – mannose (a sugar) also had a role in the process.

Specifically, they discovered that the fungus is more likely to be taken up by lung cells when it has been growing for a few hours compared to when it’s just a fresh spore. Swollen fungal spores that were locked at 3 and 6 hours of germination were 2-fold more readily internalised than those locked at 0 hours. They also identified that a sugar molecule called mannose on the surface of the fungus plays a big role in this process. 

Mannose is a type of sugar molecule that can be found on the surface of various cells, including those of pathogens like Aspergillus fumigatus. This sugar plays an important role in the interactions between the fungus and the host’s cells, particularly the AECs lining the lungs. In a healthy immune response, mannose on the surface of pathogens can be recognised by mannose receptors on immune cells, triggering a series of immune responses aimed at eliminating the pathogen. However, Aspergillus fumigatus has evolved to exploit this interaction, allowing it to adhere to and invade lung cells more effectively. The presence of mannose on the fungus’ surface facilitates its binding to mannose-binding lectins (MBLs) (proteins that bind specifically to mannose) on the surface of lung cells. This binding can promote the internalisation of the fungus into the lung cells, where it can reside and potentially cause infection.

The research highlighted the possibility of manipulating this interaction as a means to combat fungal infections. By adding mannose or mannose-binding lectins like Concanavalin A, researchers could significantly reduce the fungus’s ability to invade lung cells. This reduction was accomplished by essentially “competing” with the fungus for the binding sites on the lung cells or by directly blocking the fungal mannose, thereby inhibiting the interaction that facilitates fungal infection.

Why does it matter?

Understanding these interactions gives us important insights into how our lungs protect us from fungal infections and what goes wrong in people who are vulnerable to such infections. This knowledge could help in creating new treatments against pathogens like Aspergillus fumigatus.

You can read the full abstract here.