Aug 20, 2017 | Updated: 10:39 AM EDT

Red Blood Cells Reveal Trap Door for Malaria—How This Parasite Finds Its Way In

May 07, 2015 02:47 PM EDT

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In breaking news out of Harvard, researchers announce today they may have identified a crucial link in the deadly chain of malaria infection - the red blood cell's entry portal for the lethal parasite, Plasmodium falciparum. Their discovery may pave the way for a much anticipated therapy - a vaccine.

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Scientists at Harvard's T. H. Chan School of Public Health have identified a protein, known as CD55, which resides on the surface of human red blood cells and serves as a point of entry for the Plasmodium falciparum parasite, the most lethal of the four species of Plasmodium that cause malaria in humans.

In collaboration with the Broad Institute, the Harvard Medical School conducted a five-year study to investigate just how malarial parasites invade a host's red blood cells.

"Plasmodium falciparum malaria parasites have evolved several key-like molecules to enter into human red blood cells through different door-like receptors. Hence, if one red blood cell door is blocked, the parasite finds another way to enter," said senior author Manoj Duraisingh, John LaPorte Given Professor of Immunology and Infectious Diseases at Harvard Chan. "We have now identified an essential host factor which when removed prevents all parasite strains from entering red blood cells."

Entry into a host's red blood cells is just one step in the complex life cycle of the malarial parasite. An infected mosquito bites a human and injects the pathogen, which travels first to the liver and reproduces. This stage of infection can last from weeks to years, but eventually the pathogens are released into the blood stream, where they infect the red blood cells. The infected blood cells eventually burst, releasing another wave of pathogens that then invade additional red blood cells. The researchers at Harvard hope to break this deadly cycle by blocking the invasion of red blood cells altogether.

Should they succeed, it would mean millions of lives saved, for malaria is one of the most pernicious diseases on the planet. It is found in over 106 countries and territories and over half the world's population live in areas at risk of transmission. Each year over 200 million cases emerge, leading to over a million deaths worldwide, mostly in Africa. Children and pregnant women are most at risk; children, because of their immature immune systems and pregnant women, because of the normal suppression of the immune system during pregnancy. And when the pregnant are infected, the results are spontaneous abortion, fetal death, premature birth, and low birth weight.

"The discovery of CD55 as an essential host factor for P. falciparum raises the intriguing possibility of host-directed therapeutics for malaria, as is used in HIV," said lead author Elizabeth Egan, research fellow on the Harvard team and an instructor in pediatrics at Boston Children's Hospital. "CD55 also gives us a hook with which to search for new parasite proteins important for invasion, which could serve as vaccine targets."

The full report for this ground-breaking research appears online today in the journal Science.

 

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