The worm that turned
After monitoring the local population for some time it turned out that the worms had a cunning way to deal with the human immune system. They weren’t so much avoiding the body’s defences; instead they were stimulating the part of the immune system that is responsible for keeping the rest of it under control.
‘The driving force of any immune response is a cell called the T-cell,’ explains Professor Pritchard. ‘T-cells called T-helper 1 fight bacteria – and if that part of the immune system over-reacts you get diseases like Crohn’s, psoriasis, and rheumatoid arthritis. On the other side are T-helper 2 cells which fight worm infection, but when this side of the immune system overreacts you get allergies. In the middle is a more recently discovered population of T-cells called regulatory T-cells. These keep everything in check. Our hypothesis is that the worms are expanding the population of regulatory T-cells to down-regulate the rest of the immune response.’
So, if the worms could dampen an otherwise healthy immune system, could they be used to calm down an overactive one?
Evidence from Professor John Britton of the Division of Respiratory Medicine seemed to suggest that they could. At the time, Professor Britton had just finished a study in Ethiopia which showed a link between hookworm infection and a reduced incidence of wheeze from dust mites – the most common asthma-causing allergen in the UK.
Buoyed by the mounting evidence, and with the first phase of the trial complete, the next stage is to recruit volunteers with hayfevertype allergies for the next phase of the study.
‘We have people coming into the labs now to be infected with 10 hookworm larvae each,’ say Professor Pritchard. 'By the next pollen season we hope there’ll be an alleviation of symptoms, and if there’s any indication of success we’ll move into asthmatic patients.’ A parallel study by colleagues in the Division of Gastroenterology is also underway, using the same technique in a study of Crohn’s disease.
The team is keen to stress that 10 hookworms isn’t enough to cause injury, and since they don’t multiply inside the human body, the infection won’t get out of control. More importantly, it can be cured with drugs at any time.
It’s early days, but the long-term goal of this research is to provide alternatives for current immune suppressant drugs, used to tackle autoimmune diseases and to prevent rejection of organ transplant. The drugs currently used suppress the entire immune system, which leaves the patient open to secondary infection, and drug companies are keen to develop more targeted alternatives.
‘If we can work out how these regulatory T-cells are switched on then the pharmaceutical industry can follow that up,’ says Professor Pritchard.
And, since his team already has some experience in this area, it’s in a good position to find new leads. Earlier this year they identified how certain molecules released by the infectious Pseudomonas bacterium can be used to suppress parts of the immune system.
This is leading to new work in the treatment of the autoimmune disease diabetes, where trials using a purified molecule have proven to have an effect on the immune system of a host. This research was carried out with Professor Paul Williams in the University’s Institute of Infections, Immunity & Inflammation and the team was also the first to reveal how enzymes and antibiotics released by maggots in an open wound could actually stimulate the body’s own healing process.
‘We’re working on a “drugs from bugs” enterprise here,’ he says. ‘Maybe there’s a message in the parasite.’
Further information
Professor David Pritchard T: 0115 951 6165
e-mail: david.pritchard@nottingham.ac.uk
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