Malaria is a disease caused by single-celled parasites from the Plasmodium group, transmitted to humans through infected mosquitoes’ bites. Once the parasites enter the bloodstream, they are in danger of being recognized as intruders (and promptly destroyed) by circulating immune cells.
Fascinatingly, Plasmodium have a sneaky strategy for avoiding capture up their sleeves. They cloak themselves in red blood cells, creating flower-shaped shields to invade the body in stealth mode, deftly slipping past immune surveillance.
“These flower-like rosette structures are stable and can withstand shear force as high as that of an artery,” said infectious disease expert Laurent Renia.
“This means that these stable RBC clumps can hamper blood flow in our capillaries, leading to severe pathological consequences. The rosettes also shield the parasites from being recognized and targeted by our immune system.”
According to WHO estimates, there were 228 million new malaria cases resulting in 405,000 deaths in 2018. The majority of those impacted were children under the age of five. Understanding the molecular basis of Plasmodium’s tactics for infection—of which much is still unknown—is critical for designing strategies to combat malaria.
Renia and colleagues discovered that rosette formation was triggered by certain biochemical factors secreted by immune monocytes. The team performed mass spectrometry analysis and various antibody neutralization assays on blood samples from malaria-infected individuals. They observed that the presence of insulin-like growth factor binding protein 7, or IGFBP7, signaled to Plasmodium that it was time to take cover by hiding in red blood cell rosettes.
This form of rosette formation had, until now, never been described and was found to be much more effective from the parasite’s perspective. Here, multiple immune phacocytes were required to eliminate a single rosette, meaning that there are more chances for the parasite to get the upper hand. “The ability to perceive a phagocyte’s secreted IGFBP7 as a signal of ‘approaching threats’ and to respond by rosetting may provide survival advantage to the parasites,” wrote the authors.
“Now that we have deciphered an important role for rosetting phenomenon as an immune-evasion strategy by the parasites, we hope that this can inspire more researchers to solve the puzzles behind the pathogenesis of a parasitic infection that has cumulatively taken billions of lives since the beginning of civilization,” commented Renia.