Human lung cells: a defence against fungal spores

Every day we inhale hundreds of fungal spores but these in healthy individuals are efficiently eliminated by specialist immune cells called phagocytes which engulf and kill them. However, some human illnesses interfere with this defence mechanism, increasing susceptibility to fungal diseases.

A specialist lung tissue called the epithelium is the first line of contact between the inhaled spores and us, the host. We are working to understand how the lung epithelium interacts with the spores of a common mould called Aspergillus fumigatus.

We have generated fluorescent Aspergillus and combined this with fungal and host specific dyes to directly visulaise this interaction. We have discovered that epithelial cells ingest fungal spores and kill them.

This might provide a critical defence mechanism which is acting while we breathe, and before even phagocytes arrive at the site of the infection.

We are now trying to work out how epithelial cells grab and ingest fungal spores, by using fluorescent fungal mutants and targeted elimination of host proteins.

Once we understand this process in detail we can design new therapies to assist a quicker elimination of the dangerous fungal spores we all inhale on a daily basis.

Dr Margherita Bertuzzi works in Dr Elaine Bignell's lab at the University of Manchester

Aspergillus fumigatus, a mold hard to kill

We all breathe into our lungs thousands of fungal spores every single day and among them we encounter Aspergillus fumigatus spores. Fortunately our immune system is extremely good at killing these spores. However, if the individual’s immune system is not working properly Aspergillus fumigatus can survive and become life-threatening.

Unfortunately there are few anti-fungal drugs available to treat this killing machine and understanding of how they work is a limited.

Using advanced time-lapse microscopy I have been studying the main cellular adaptations that allows Aspergillus fumigatus to overcome the attack of caspofungin, a commonly used anti-fungal drug.

My research will provide a better understanding of the way in which caspofungin works in inhibiting Aspergillus fumigatus growth and infection. And this might provide new insights into how the design of novel anti-fungal drugs might be improved.

Sergio Valasquez works in Professor Nick Read's lab at the University of Manchester.