Malaria is a disease transmitted by mosquitoes that are vectors of parasites in the genus Plasmodium. Scientists from the Institut Pasteur, in collaboration with specialized physicists in Brazil and Germany, have elucidated the search strategy used by parasites to reach the bloodstream.
Parasites in the genus Plasmodium are responsible for malaria. They infect humans via mosquitoes that have themselves been infected. Once the parasite has been deposited in the skin through a bite, it moves through the tissue looking for a blood vessel and must then cross the vessel wall to enter the bloodstream and then the liver, where it initiates infection. Parasites gradually lose their ability to migrate through tissue and only have a limited time (1 to 2 hours) to locate and invade blood vessels.
Strategic movement of the malaria parasite revealed
In a recent study published in the journal Nature Communications, Rogerio Amino, Head of the Institut Pasteur's Malaria Infection & Immunity Unit, and Pauline Formaglio, a postdoctoral research fellow in his term, revealed the strategy implemented by parasites to optimize their movement in search of blood vessels. Parasites use two types of motility to search the cutaneous environment:
- high motility characterized by phases of high-speed movement virtually in a straight line as they move through the tissue;
- low motility characterized by slower movements near blood vessels that enable them to scan the local blood vessel surface.
"Our research demonstrates that parasites wanting to access the bloodstream do not just enter at a random location in the vascular tree. They prefer to cross the blood vessel wall at regions characterized by the presence of cells known as pericytes, which surround blood vessels and regulate their formation and function," explains Rogerio. So the alternating high-motility phases through tissue and low-motility phases near blood vessels successively optimize the parasite's chances of finding a blood vessel and then a preferred entry site in the bloodstream. This search strategy enables 20-30% of parasites to join the bloodstream in the limited time they have and contributes to the effective transmission of malaria, which affects 250 million people and still causes more than 500,000 deaths every year.
A new avenue to improve malaria prevention
The skin stage of infection, when the parasite migrates from the skin to the bloodstream, represents a promising target for prophylactic and vaccine treatments. It is known, for example, that antibodies directed at the most abundant parasite surface protein can slow, immobilize or even kill parasites in the skin, representing one of the first lines of defense against parasites. Understanding why parasites prefer to use pericyte-associated sites to access the bloodstream and identifying any specific molecular interactions between pericytes and parasites could open up new avenues to improve existing preventive approaches aimed at blocking the parasite in the skin.
The Institut Pasteur's technology core facilities played a key role in this study by offering access to the biological material, equipment and infrastructure needed for the experimental research.
The parasite's trajectories were analyzed in collaboration with physicists at several universities in Brazil (the Universidade Federal do Paraná, Universidade Federal de Pernambuco and Universidade Federal do Rio Grande do Norte) and Germany (the Max Planck Institute for Brain Research), with the support of funding from the Brazilian government aimed at promoting international collaboration.
Plasmodium sporozoite search strategy to locate hotspots of blood vessel invasion, Nature Communications, May 23, 2023.