Dutch scientists discover how the malaria parasite’s invisibility cloak works (and can remove it)

The immune system of mosquitoes is unable to deal with the malaria parasite. Now scientists finally know why.

in the paper PNAS An international team of researchers – including Dutch scientists – describes an enzyme that actually makes the malaria parasite invisible to the mosquito’s immune system. “The parasite’s QC enzyme alters the proteins on the parasite’s outer surface, so that immune cells do not recognize the parasite and therefore do not get rid of it,” explains researcher Chris Jansey, affiliated with Leiden University Medical Center.

From mosquitoes to humans
Malaria is a serious infectious disease transmitted to humans by mosquitoes. The disease is caused by parasites. The spores of these parasites are found in the salivary glands of a mosquito and when a mosquito bites a human it ends up in the bloodstream of its human victim. The spores travel through the bloodstream to the liver, where they settle and multiply. The journey from the mosquito’s salivary glands to the human liver is undisturbed, because neither the mosquito’s immune system nor the human immune system “sees” the parasites and therefore takes no action to disinfect them.

From cancer research to malaria research
But how exactly do parasites – or more precisely: their tracks – make themselves invisible to the immune system? This was unclear for a long time. Even skin researcher Ferenc Scheren rang the bell with Jhansi. Sherine recently discovered a specific enzyme that ensures that cancer cells are not detected by the human immune system. It turns out that malaria parasites have a similar enzyme. With Scheeren’s encouragement, Janse researched this similar enzyme.

And successfully. Because experiments show that this enzyme actually ensures that the mosquito’s immune system doesn’t detect parasites. And when researchers genetically modified mosquitoes in a way that lacked this specific enzyme, the immune system suddenly detected the malaria parasites and they were encapsulated and cleared by immune cells. “We’ve never seen anything like this,” Jancy says. “We genetically engineered many different malaria parasites in the lab that lacked the enzymes, in no other case was the mosquito able to clean up the live parasites on its own.”

special discovery
So a special discovery. Especially because it came through cancer research. The protein that Sherine examined in the course of this research also modified the outer surface of cancer cells to prevent these cells from being detected by the immune system. Remarkably, the single-celled malaria parasite uses a similar strategy. “We don’t often see that similar enzymes arise at two different independent moments in evolution,” says Jans.

Malaria is caused by malaria parasites. There are five types of malaria parasites, two of which – Plasmodium falciparum and Plasmodium vivax – cause the most problems, especially in Africa, but also in Asia and South America. The first symptoms usually appear within 10 to 15 days after the bite of the malaria mosquito. People can then have a fever, headache, and chills. Without treatment, the infection can be fatal, especially to young children, pregnant women, and people with weakened immune systems. According to the World Health Organization, there were 241 million cases of malaria in 2020. In the same year, an estimated 627,000 people died from the disease.

Serum
It is hoped that the discovery of the enzyme will play a role in the fight against malaria. In this context, Jancy is working on a malaria vaccine that contains a weakened malaria parasite. Preliminary clinical research shows that the vaccine triggers an immune response that can at least slow down the disease. However, researchers hope to eventually develop a vaccine that can actually prevent the disease.

However, in the meantime, more research is being done on other ways to stop malaria. Research into the protein that makes the malaria parasite invisible to the mosquito’s immune system is a good example of this. It provides new starting points for reducing the transmission of malaria from mosquitoes to humans. It may also have implications for treating malaria patients. In the future, researchers hope to find out if the malaria parasite also uses the same enzyme to remain invisible to the human immune system.