Dealing with diversity – immune responses to fungi

Fungi are everywhere. They’re present in the air, in our food, some even live inside our bodies. But most of us rarely think about diseases caused by fungi. This is because our defences do a really good job in keeping them in check.

However for millions of people whose immune system are defective fungi can cause serious infections that are hard to treat and can be life threatening.

A group of cells called phagocytes play a key role in keeping us safe from fungi. They normally patrol our body so when there’s a breach they are the first to respond. Their function is to seek eat and destroy microbial intruders.

But no all fungi are alike. My Ph.D. project aims to understand how phagocytes tackle such different targets. So far I have found there are huge differences in the rate at which various different fungi are engulfed by phagocytes.

The speed of these processes depends on the chemical composition of the fungi, whether they are alive or dead, and whether they are coated with human proteins that help to mark them as intruders.

Understanding the basic biology behind these processes is the first step towards developing new treatment strategies.

Maria Fernanda Alonso works in Professor Neil Gow's lab at the University of Aberdeen.

The heat is on; cooling down the response to Aspergillus

My research is focused on infections caused by Aspergillus, which is present in the environment all around us. We each inhale hundreds of fungal spores every single day, and for the majority of people this doesn't cause any problems, but for people whose immune system isn't working properly Aspergillus can cause serious, even life threatening, infections.

One group of patients who are at particular risk of Aspergillus infection are people with a rare inherited immune deficiency called chronic granulomatous disease, or CGD.

For these patients infection with Aspergillus is frequently fatal, even with appropriate anti-fungal treatment.

My research so far suggests that rather than not mounting a sufficient immune response, the CGD immune system actually over-reacts to Aspergillus, causing significant tissue damage but without clearing the fungal infection.

We're therefore looking at whether we can use new treatments aimed at reducing inflammation alongside conventional anti-fungal drugs to improve the outcome of these devastating infections for CGD patients.

Dr Jill King works in Professor Adilia Warris's lab at the University of Aberdeen

The host-pathogen struggle for nutrients

We can view an infection as a battle between the human host and the microbial invader. The outcome of which decides whether the host remains healthy or succumbs to disease. As this battle rages microbial invaders use their hosts as a source of nutrients.

However, the human body has evolved complex systems to limit access to certain essential nutrients in an attempt to starve the invading microbes and prevent disease.

We call these processes nutritional immunity. Therefore, to win the battle and cause disease microbial pathogens must have evolved strategies to thrive in a nutritionally restrictive environment within its infected host.

We are interested in exploring how the human fungal pathogen Candida albicans adapts to limitations to essential trace nutrient zinc. We have identified specific coping mechanisms that are adopted by this fungus in order to deal with nutritional immunity. In response to zinc starvation, Candida albicans dramatically changed their cell shape.

We therefore want to know how this change is regulated and what impact it has on the progression of infection with the ultimate aim to therapeutically manipulate the system and push the balance back in favour of the human host to prevent disease.

Dhara Malavia works in Dr Duncan Wilson's lab at the University of Aberdeen.

Detecting and Destroying Fungi with Antibodies

Every year more than one million people die from a fungal infection. This figure is higher than the number of lives taken by malaria and almost as many as those claimed by HIV or tuberculosis. To make a difference in this area we urgently need to address two key issues.

First of all, we need to diagnose fungal infections more accurately and earlier on during the course of disease as we know that every day we fail to make an accurate diagnosis, we lose more and more of our patients.

Secondly, we need to develop the first vaccines for fungal infection and get them into the clinic and develop new antifungal drugs which are more effective at treating and killing the fungus and have fewer side effects.

With these in mind, my research project focuses on developing antibodies which have been cloned from the DNA taken directly from human antibody producing cells. therefore making them more compatible with our own immune systems.

These antibodies have great potential to make a huge impact in the way we diagnose and treat fungal infections in the future, ultimately improving patient quality of life and saving more lives.

Dr Fiona Rudkin works in Professor Neil Gow's lab at the University of Aberdeen.