How sickle-cell anaemia mutes severe malaria

Washington: Scientists at Heidelberg University Hospital have finally solved the mystery - why people with a hereditary mutation of the red blood pigment haemoglobin - as is the case with sickle-cell anaemia prevalent in Africa - do not contract severe malaria?

A degradation product of the altered hemoglobin provides protection from severe malaria.

Within the red blood cells infected by the malaria parasite, it blocks the establishment of a trafficking system used by the parasite’s special adhesive proteins – adhesins – to access the exterior of the blood cells.

As a result, the infected blood cells do not adhere to the vessel walls, as is usually the case for this type of malaria.

In the 1940s, researchers already discovered that sickle-cell anemia with its characteristic blood mutation was particularly prevalent in certain population groups in Africa. They also survived malaria tropica, whose course is usually especially virulent.
The scientists team headed by Prof. Michael Lanzer of the Department of Infectious Diseases at Heidelberg University Hospital compared the blood cells with normal haemoglobin and two haemoglobin variants (haemoglobin S and haemoglobin C), which occur in around one-fifth of the African population in malaria-infected areas.

In doing so, the scientists used high-resolution microscopy techniques such as cryoelectron tomography to discover a new transport mechanism.

The parasite uses a certain protein (actin) from the cytoskeleton (cellular skeleton) of the erythrocytes for its own trafficking network.

“It forms a completely new structure that has nothing in common with the rest of the cytoskeleton,” explained Dr. Marek Cyrklaff, group leader at the Dept. of Infectious Diseases, Parasitology.

“The vesicles with the adhesins reach the cell surface of the red blood cells directly via these actin filaments,” he said.

In contrast to erythrocytes with the two haemoglobin variants, here only short pieces of actin filaments are found. Targeted transport to the surface is not possible.

“With these results, we have now described a molecular mechanism for the first time that explains this haemoglobin variant’s protective effect against malaria,” Lanzer added.

The research study has been published in the journal Science, appearing initially online.


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