'Stickiness' of blood cells key to malaria protection
Researchers have found a possible explanation for why some West African children don't develop the deadliest form of malaria — the children's genes prevent infected red blood cells from becoming too 'sticky'.
The team, led by Thomas Wellems of the US National Institute of Allergy and Infectious Diseases, published its results in this week's issue of Nature.
The team's research focused on the genes that produce haemoglobin — the protein that allows red blood cells to carry oxygen.
Haemoglobin exists in several forms, depending on which genes a person has; some people have two A genes, some have two C genes and some people have one copy of each gene.
The 'A' form of the gene is most common, but in parts of West Africa one-quarter of the population has at least one C gene.
In the past, scientists have noted that children with at least one C gene are less likely to develop deadly 'cerebral' malaria; a form of the disease in which the parasite accumulates in the brain. But until now nobody has known how having the C form of haemoglobin protects the children.
When the malaria parasite infects red blood cells, it changes their structure by placing 'knob-like' proteins on the cell surface.
top to bottom: surfaces
uninfected red blood cell,
infected AA cell, and
infected CC cell
These proteins, known as PfEMP-1, make the cells stick to each other and to the walls of blood vessels. This causes the cells to accumulate in small blood vessels rather than be carried by the blood to the spleen, where infected cells would normally be destroyed.
The researchers found that on blood cells from people with two A genes (and so no C genes) the PfEMP-1 protein was evenly distributed across the cells' surface.
In this formation the proteins act like hooks, causing infected cells to get stuck in tiny blood vessels and avoid being removed from the bloodstream.
Wellems explains that when infected red blood cells stick to blood vessels it causes an inflammation that can increase the severity of malaria symptoms.
Cells with at least one C gene were much less 'sticky' in the researchers' experiments.
Cells with one A and one C gene that were infected with malaria in the laboratory were 25 per cent less likely to stick to the walls of blood vessels, and 33 per cent less likely to stick to uninfected blood cells.
Cells with two copies of the C gene rarely stuck to other blood cells and did not stick to blood vessels at all.
The researchers also looked at how much PfEMP-1 was being produced by infected red blood cells.
They noticed that the amount produced by cells with two C genes varied depending on which type of malaria parasite was used to infect them.
These results indicate that the protection the C genes offer will vary depending on which strain of malaria is predominant in an area.
Click here for a larger, annotated version of the top illustration
Link to full paper in Nature