A Maynooth researcher is using insects rather than laboratory animals to study how fungal spores can cause infections in humans, writes Claire O'Connell
On the face of it, we don't appear to have much in common with insects, but scratch the surface and our basic immune systems are remarkably similar. Thanks to that likeness, researchers in Maynooth are now using moths to figure out how disease-causing fungi can undermine human defence systems and cause potentially fatal infections.
"The innate immune response in mammals is equivalent to the insect immune system, they are 99 per cent similar," explains Dr Kevin Kavanagh, a senior lecturer at NUI Maynooth's biology department. "About six or seven years ago we established that if you use fungal pathogens in insects, you can get the same result as using those pathogens in mice."
Insects are cheap, easy to work with and provide a good model for the basic immune systems in mammals, including mice and humans, according to Dr Kavanagh, whose work is funded by the Higher Education Authority. "We started working with a moth called Galleria," he says. "We can get results in two days whereas if you are using mice it takes up to five weeks. And of course there's the whole ethical thing - insects don't have as developed a nervous system and there are no ethical problems with using them."
By infecting Galleria larvae with a potentially fatal fungus called Aspergillus fumigatus, the Maynooth researchers have figured out how the fungus breaks down its host immune system's frontline defences against invaders.
Aspergillus is common around building sites, gardens and farms and most of us inhale around 100 of its spores each day. Healthy immune systems can cope with that load, explains Dr Kavanagh. However the fungus can pose a serious problem for people with compromised immune systems, such as people with cystic fibrosis or patients undergoing chemotherapy or transplant. "When the fungus gets into the lungs of humans, particularly if their immune system is damaged or they are immuno-compromised, it produces toxins, which are like chemical weapons," says Dr Kavanagh.
"They neutralise the immune response in the lung initially and then they can neutralise the whole body response to allow the fungus to grow. We were interested in studying these toxins in the insect because we could then extrapolate the results from that to the mammal without having to use mice or humans."
By infecting insect larvae in the lab, the Maynooth team discovered that the Aspergillus fungus releases a chemical called gliatoxin, which stops frontline cells of the immune system from swallowing and destroying the invader, explains Kavanagh. "It knocks out one of the main soldiers that the body has," he says.
Dr Kavanagh and Dr Seán Doyle at Maynooth have been looking at the genes involved in making gliatoxin, with a view to eliminating the chemical weapon at source. "We are looking at developing ways to knock out the toxin production in the body," says Dr Kavanagh, who adds that they have already identified some genes involved.
Therapy to knock out key toxin genes in the fungus as it is trying to invade could be a lifesaver for at-risk patients who inhale the fungal spores, according to Dr Kavanagh. "Aspergillus infection is one of the biggest killers of liver transplant patients," he says. "If you could give the patient something so that if they did get a fungus it wouldn't produce toxin, well then you would have a patient with a better chance of surviving."