Taking control of the blunt force of parasitic worms to prevent asthma
Parasitic worms protect children from allergies. They do this by changing the children's immune system. Prof.dr. Rick Maizels has made amazing discoveries on how this works. ‘Our immune system is meticulously controlled as it can also do harm. The worm has no such concern. So it works bluntly.’ And in time, these blunt tools may also help us prevent asthma.
‘Science is a slow proces when you’re in the middle of it,’ Rick Maizels says. ‘But looking back you see the progress. It is always fun to achieve this.’ And he should know. Earlier it was observed that school children infected with parasitic worms had lower risk of developing allergies. Then Maizels was the first to prove the worms actually caused this. Moreover, he discovered worms did this by changing the immune response. How, was yet a mystery.
Trick to survive
‘Since then, we have learned a great deal,’ says Maizels, now a renowned scientist on parasitic worms and leader of a research group in the Asthma Prevention Consortium. Our immune system is very strong in attacking parasites. But parasitic worms have developed a trick to survive. They release some 2.000 different proteins. And through these, they suppress our immunesystem. As a side effect, inflammation in response to allergic substances like house dust mite does not occur. And in mice parasitic worms also resulted in protection against asthma, Maizels showed.
Maizels: ‘Together with other consortium researchers, like prof.dr. Henry McSorley, we try to find out which worm proteins play a leading role at each phase of the immune response. And how this works on a molecular level. This way we can learn how to protect children from developing asthma.’
Make a difference
‘My research is quite fundamental, but I don’t want it to be just for the record. The consortium has a great ambition to find treatments for patients and make a difference. And I am eager to contribute to this.’
Maizels and McSorley both study how worm proteins suppress the immune response. But they each have a different approach. For instance, McSorley takes all of the released proteins and tries to find out which of these interfere with the immune system (and how). Where as Maizels works on a small number of so called target proteins (known to have some involvement), and tries to pinpoint how they interfere with the immune system. ‘Also, we study the effects from the opposite direction. Of all the immune molecules involved in the allergic response, we unravel how the worm proteins interact with these.’
Recent years Maizels did some amazing discoveries. For instance, parasitic worms have copied certain molecules of the immune system that suppress a specific immune protein. This immune protein, TGF-beta, plays a huge role in controlling inflammatory responses to allergic substances. ‘But the copied molecule appears to be more effective than the human version. This is also the case with worm molecules interfering with eosinophils.’ These are a type of white blood cells that causes inflammation and swelling of the airways. They expand in specific types of asthma and in humans infected with paracitic worms. Maizels proved worm proteins forestall eosinophil production.
So worm molecules suppress the immune system in different ways and on different levels. Interestingly, there is a similarity between these pathways: many of the worm proteins appear to have a stronger effect then their hosts’ own molecules.
The reason for this is that the worm is not restricted, Maizels suspects. ‘And the immune system is. It can also do harm. Therefor, it has to be meticulously controlled to achieve a very precise effect under strict conditions. But the only concern of the worm is to shut down the immune response. So it does this bluntly.’
Treatment: apply blunt force safely
But how does this bring us closer to preventing asthma? ‘The many worm proteins offer many possibilities for treatments. If we find out which parts of the proteins are responsible for the strong immune suppression, we can try to synthesise these in the lab in a form our immune system does not see as foreign. This way we can apply the blunt force safely.’
Getting there is a ‘big mountain to climb’, Maizels says. ‘The work is not difficult but time consuming: there are many possibilities to test.’ Working in the consortium does take him up the mountain faster. ‘Together we work on different subjects, from unprocessed cow’s milk and farm dust to worms. It is plausible we find common mechanisms.’ And what would be the ideal outcome? ‘To use proteins from worms to replicate the protective effect of cow’s milk or farm dust against asthma. Working close together in the consortium may enable this.’
Text: Karin Postelmans