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Researchers discover how malaria parasite survives in mosquitoes

Researchers from Leiden University Medical Center (LUMC) have discovered how malaria parasites escape the immune system of mosquitoes. The so-called QC enzyme changes proteins on the outside of the malaria parasite such that the immune cells are unable to recognise the parasite. As a result, the parasite can spread freely amongst humans via the mosquito.

Malaria parasites, or more specifically sporozoites, wait in the salivary glands of the mosquito until it bites a human. They travel through the blood to the liver, where they nestle and multiply. They can do this undisturbed because they escape both the mosquito’s and the human’s immune systems. Parasitologist Chris Janse and colleagues have now figured out how the parasite fools the mosquito’s immune system. ‘The parasite’s QC enzyme alters proteins on the outside of the parasite, which prevents immune cells from recognising the parasite and thus eliminating it.’  

Malaria parasites that lacked the QC enzyme were recognised by mosquitoes’ immune cells.

Mosquito versus parasite

In the scientific journal PNAS Janse and colleagues write that malaria parasites that lacked this enzyme were recognised by mosquitoes’ immune cells, which encapsulated and eliminated them. ‘We’d never seen anything like it before,’ says Janse, who is mainly working on developing a malaria vaccine with genetically weakened parasites. ‘We used genetic modification in the lab to produce lots of different malaria parasites that lacked various enzymes, and in no other instance could the mosquito eliminate living parasites on its own.’

Cancer cells and parasites

The tip to look at the QC enzyme in malaria parasites came from an unexpected source. Ferenc Scheeren, a researcher at the Department of Skin Diseases, had just demonstrated that a specific enzyme prevents cancer cells from being recognised by the human immune systemHe saw a similar enzyme in malaria parasites. It now appears that the single-celled malaria parasite and human cells use the same strategy to escape the immune system: using QC enzymes to alter proteins on the outside of cells. And that is rather unique, says Janse. ‘We don’t often see similar enzymes arise at two different independent moments in evolution.’ 

Janse and colleagues from the LUMC’s Centre for Proteomics and Metabolomics worked on this study with researchers from the National Institutes of Health in the United States and a research group from Japan. They examined the parasite protein that the enzyme changes.

‘The knowledge offers new perspectives on how to contain malaria’

New strategies

Janse believes this discovery offers new opportunities to inhibit malaria’s transmission by mosquitos. He won’t be researching this, however, because the LUMC research group’s focus is on developing a malaria vaccine. But he is convinced that it is important knowledge for other research groups. ‘It offers new perspectives on how to contain malaria,’ he says. ‘We’re going to investigate whether the malaria parasite also bypasses the human immune system in this way.’

Photo: Pexels/Jimmy Chan

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