A new model study system using the red blood cells to study malaria invasion; were the new model system that using red blood cells grown in the laboratory; to study how malaria parasites invading the red blood cells. Study providing a powerful new research tool for the identification of key host proteins and their domains that are involved in parasite infection. It will facilitate attempts to understand and disrupt the mechanism of red blood cell invasion by malaria parasites.
But the scientists used a cell line recently developed in Bristol which can produce unlimited numbers of immature ‘progenitor cells’ that can be pushed to produce new red blood cells (reticulocytes) in the laboratory. But using these cells, they were able to show that red blood cells generated using this technique can support both invasion by and intracellular development of Plasmodium falciparum, the malaria parasite that is responsible for around 200 million new infections and half a million deaths per year worldwide.
Red blood cells
By using CRISPR-Cas9 to edit the genome of the immature cells; the team were also able to remove a protein called basigin that is important for invasion and normally present on the surface of red blood cells; and show that the reticulocytes generating from this editing line were completely resistant to invasion. Reintroducing the basigin gene into the editing cells restoring invasion to normal levels.
But this important work showing that these cells can be using to remove; and replace different red blood cell proteins; and assess how their absence or alteration affects the ability of the parasite to successfully invade. But the ability to alter protein expression in the red blood cell and study the effect that these changes have on parasite invasion or development is hugely exciting.
New potential avenues
This system has opened up many new potential avenues of research; that should allow us to better understand the mechanism by which the malaria parasite is able to successfully invade the red blood cell; and the specific roles that host cell proteins play in this process. But it also showing that our reticulocytes producing from the cell line are recognising; by the parasite just the same as reticulocytes produced in the body. This is important as it providing further evidence; that the cells are manufacturing correctly in the laboratory.
But this demonstration of reticulocytes derived from cell lines; supporting malaria invasion will provide an important new tool to better understand; how the malaria parasite invades red blood cells. But ultimately, we hope that this work will lead to the development of new therapeutic strategies for malaria. These data establish the use of reticulocytes derived from immortalized erythroblasts; as a powerful model system to explore hypotheses regarding host receptor requirements for P. falciparum invasion.