Malaria has been outsmarting the human immune system for centuries.
Now, using real-time imaging to track malaria infections in live mice, researchers have discovered one of the parasite's sneakiest tricks--using dead liver cells to cloak and transport itself back into the bloodstream after leaving the liver.
Robert Minard, a Howard Hughes Medical Institute (HHMI) international research scholar, and his postdoctoral fellow, Rogerio Amino, at the Institut Pasteur in Paris, filmed the malaria parasite as it transitioned from infecting liver cells to infecting red blood cells. During this stage of the parasite's life cycle, the classic symptoms of malaria - high fevers and chills - are triggered in people who are infected.
Minard and Amino collaborated with Volker Heussler at the Bernhard-Nocht Institute for Tropical Medicine in Hamburg, Germany. Their images of the parasite sneaking back into the host's bloodstream--published in advance online in Science Express on August 3, 2006, and scheduled for September 2006 publication in Science--clear up a long-standing puzzle about the malaria parasite's life cycle. The discovery could lead to new ways of treating malaria, a disease that infects 300 million people per year and kills 1 million.
"The parasite has evolved this complex structure. The best image to describe it is the Trojan horse, because it both transports the parasites and camouflages them," said Minard. Like the ancient Greek warriors who hid inside a giant hollow horse to gain entry to Troy, the malaria parasites wrap themselves in a structure made of liver cell membrane. This membrane cloak enables them to sneak past immune cell sentinels and return to the bloodstream.
The malaria parasite, Plasmodium falciparum, has a complex life cycle. It passes from a mosquito's saliva to a human's blood, and then travels to the liver, where it infects and kills liver cells. After it leaves the liver, the parasite moves back into the bloodstream to infect and kill red blood cells. The rupturing of blood cells causes the worst symptoms of the infection, which can be deadly to children, pregnant women, and others with weak immune systems.
After leaving this trail of cellular death and destruction in its wake, the parasite is finally taken up again from the blood when another mosquito bites. Then it reproduces and waits for the mosquito to bite again to infect another person.
Researchers have long assumed that the form of the parasite that infects red blood cells, called a merozoite, was released from a ruptured liver cell and moved on its own back to the bloodstream. But studies in the laboratory have shown that the liver's resident macrophage immune cells happily gobble up free-moving merozoites.
"This was a paradox," said Minard. "We could not understand how the rate of infection could be so successful."
Heussler's research team noticed irregular protrusions on the surface of liver cells that had been grown in a culture dish and infected with malaria. So they asked Minard and Amino for help finding out whether liver cells in an infected animal developed the same protrusions.