Scientists have uncovered a purported mechanism that Plasmodium parasites use to evade mammalian host immune systems. Plasmodium protozoa cause malaria in mammals; the disease afflicts as many as 500 million people each year, roughly one million of whom die annually from its ill effects.

Masters of infectious mayhem, Plasmodium species have proven recalcitrant to study, in part because of their complicated lifecycles. Plasmodium organisms enter their mammalian hosts via bites from Anopheles mosquitoes, after which they progress though various parasitic stages, moving from the bloodstream into liver cells, back to the bloodstream, and finally into red blood cells, where they cause the characteristic fever and chills associated with malaria. One puzzling aspect of the lifecycle is how the liver-stage parasites, called merozoites, are able to avoid the phagocytic immune cells that patrol the liver and bloodstream. Working with P. berghei, however, a malarial organism infectious in rodents, Volker Heussler at the Bernhard Nocht Institute for Tropical Medicine (Hamburg, Germany) and his colleagues have elucidated what seems to be one of Plasmodium's mainstay cloak-and-dagger schemes.

According to their new research, published in the 1 September issue of Science, it seems that the merozoites hijack a staple of the immune warning system: apoptosis.

Often called 'programmed cell death,' apoptosis is a form of cellular suicide induced by certain conditions, including invasion by foreign organisms. As part of the normal apoptotic process, the cell releases calcium ions that initiate a signaling system to attract pathogen-fighting phagocytes. Heussler's team found evidence that the parasites stall apoptosis in the host cells until the protozoa reach maturity, at which time they signal the host cell to undergo a parasite-induced cell death, escaping into the bloodstream in membrane-bound vesicles termed merosomes. The merosomes are filled with thousands of merozoites and calcium pirated from the now-dying liver cells, leaving those cells unable to signal immune phagocytes and allowing the merozoites to enter the bloodstream undetected.

“We've demonstrated that the translocation of parasites occurs much earlier than originally thought,” Heussler tells Lab Animal. “That means treatment against this stage should start much earlier.” Moreover, “if we can interfere with the calcium transport to the parasite,” he continues, “I predict that the merosomes will be eliminated efficiently by phagocytes.”