The team found that red blood cells in people with the rare Dantu blood variant have a higher surface tension that prevents them from being invaded by the world's deadliest malaria parasite, Plasmodium falciparum.
Because the surface tension of human red blood cells increases as they age, it may be possible to design drugs that imitate this natural process to prevent malaria infection or reduce its severity.
Red blood cell samples were collected from 42 healthy children in Kilifi, Kenya, who had either one, two or zero copies of the Dantu gene. The researchers then observed the ability of parasites to invade the cells in the laboratory, using multiple tools including time-lapse video microscopy to identify the specific step at which invasion was impaired.
Analysis of the characteristics of the red blood cell samples indicated that the Dantu variant created cells with a higher surface tension—like a drum with a tighter skin. At a certain tension, malaria parasites were no longer able to enter the cell, halting their lifecycle and preventing their ability to multiply in the blood.
"Malaria parasites utilise a specific 'lock-and-key' mechanism to infiltrate human red blood cells. When we set out to explain how the Dantu variant protects against these parasites, we expected to find subtle changes in the way this molecular mechanism works, but the answer turned out to be much more fundamental. The Dantu variant actually slightly increases the tension of the red blood cell surface. It's like the parasite still has the key to the lock, but the door is too heavy for it to open."
The Dantu blood group has a novel 'chimeric' protein that is expressed on the surface of red blood cells, and alters the balance of other surface proteins.
evolutionary adaptations like sickle cell trait and the Dantu variant may partially explain why the mortality rate is much lower than the rate of infection.
reference
Red blood cell tension protects against severe malaria in the Dantu blood group, Nature (2020). DOI: 10.1038/s41586-020-2726-6 , www.nature.com/articles/s41586-020-2726-6