Malaria parasites, or more specifically sporozoites, wait in the mosquito’s salivary glands for it to sting a human
Researchers from the 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 in such a way that the immune cells can no longer recognize the parasite. This allows it to run its course undisturbed and spread among people via the mosquito.
Malaria parasites, or more specifically sporozoites, wait in the mosquito’s salivary glands until it stings a human. They then find their way through the blood to the liver, where they nest and multiply. It can do this undisturbed because the parasite manages to escape both the mosquito’s and the human’s immune system. Parasitologist Chris Janse and colleagues have now figured out how the parasite fools the mosquito’s immune system. “The QC enzyme of the parasite changes proteins on the outside of the parasite, so that immune cells do not recognize the parasite and therefore do not clear it.”
Mosquito versus parasite
In the scientific journal PNAS, Janse and colleagues write that malaria parasites that lacked this enzyme were recognized by the immune cells of the mosquito. These parasites were encapsulated by immune cells and then cleaned up. “We had never seen anything like it,” says Janse, who is mainly involved in developing a vaccine against malaria with genetically weakened parasites. “We genetically engineered many different malaria parasites in the lab that lacked enzymes, and in no other case was the mosquito able to clean up live parasites on its own.”
Cancer cells and parasites
The tip to take a look at the QC enzyme of malaria parasites came from an unexpected source. Ferenc Scheeren, researcher at the Department of Skin Diseases, had just shown that a specific enzyme ensures that cancer cells are not recognized by the human immune system. He saw that a comparable enzyme was also found in malaria parasites. It now appears that escaping the immune system by altering proteins on the outside of cells by QC enzymes is a strategy used by both the unicellular malaria parasite and human cells. And that is very special, says Janse. “We don’t often see that comparable enzymes arise at two different independent moments in evolution.”
For this study, Janse and colleagues collaborated with researchers from the National Institutes of Health in the United States and a research group from Japan. Together with colleagues at the LUMC from the Center for Proteomics and Metabolomics, they took a closer look at the parasite protein that is changed by the enzyme.
New strategies
According to Janse, this discovery offers new targets for inhibiting the transmission of malaria via the mosquito. Janse will not conduct any research into this himself, the LUMC research group focuses entirely on developing a malaria vaccine. But Janse is convinced that it is important knowledge for other research groups. “It offers new perspectives for the containment of malaria,” he says. “We ourselves are going to investigate whether the malaria parasite also bypasses the human immune system in this way.”
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