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‘Sugar coating’ clue to how parasitic worms dupe immune system

Posted on 6 September 2007

Sugars secreted by a parasitic worm could provide the key to how it infects the human body and how its eggs escape to spread the deadly disease schistosomiasis, according to new research by a team including scientists at the University of York.

The study, published in the September 2007 edition of Molecular and Cellular Proteomics journal, has given scientists a greater understanding of complex sugars secreted by the Schistosoma mansoni worms and how they lead to successful infection of a human host. In the long term, understanding exactly how the worm evades the host’s immune system could lead to the development of a vaccine or new treatments for schistosomiasis.

Schistosomiasis is a debilitating disease, affecting up to 200 million people in Asia, Africa and South America. The parasite enters the human body through the skin when people come into contact with fresh water where it lives. It can cause severe liver damage, blood loss and sometimes lead to death.

The research team, from Imperial College London and the Department of Biology at York, suggests that the sugars secreted by the worm are vital to the worm’s ability to hoodwink the host’s immune system. Analysing the secreted sugars using mass spectrometry, the scientists found these worms’ secretions contain a plethora of complex sugars that cannot be found in the human host.

Parasites normally try to hide from their host's immune system but some schistosome stages seem to advertise their presence

Professor Alan Wilson

Dr Stuart Haslam from Imperial College London’s Division of Molecular Biosciences, lead author of the study, explains: "Sugars secreted into the host’s skin when the worm penetrates have a key role to play in whether or not the host’s immune system recognises the worm as a threat. Much in the way that a matador uses his cloak to distract the bull and prevent personal injury, so the secretions distract the immune system and prevent the real target, the worm, being attacked."

The researchers think that one possibility of how this works is that the sugars secreted are highly immunogenic, meaning they prompt the host’s immune system to home in on them and attack. But by the time the host’s anti-infection white blood cells reach the site of the sugars, the worm itself has already moved on to another place in the body.

"Conversely, the parasite’s eggs laid in the gut wall deliberately attract the immune system through the release of these immunogenic sugars, apparently fooling the host’s immune cells into aiding their escape from the body."

Professor Alan Wilson, who headed the York research team, added: "Parasites normally try to hide from their host's immune system but some schistosome stages seem to advertise their presence. We have discovered an amazing diversity in the glycans (sugars) that they use to decorate larval and egg secreted proteins, and these molecules provoke strong immune responses.

"We believe that, for the larva that infects by skin penetration, the glycans serve to distract inflammatory cells whilst the parasite target slips away. For the schistosome egg in the wall of the intestine, the inflammatory cells that congregate, instead of killing it actually help its exit."

Dr Haslam added: "Even though our study provides us with more clues than ever before as to precisely how these worms infect a host, and we now believe these sugars are key, more scientific investigations are needed to unravel exactly how these worms infect so many people around the world each year," he added.

ENDS