New Insights into Dual-Function Proteins and Their Role in Malaria Immune Evasion and Detection

Malaria remains one of the most severe infectious diseases globally, transmitted by mosquitoes harboring Plasmodium parasites that invade human red blood cells. These infected cells are notoriously difficult for the immune system to detect and eliminate. Recent research from the University of Osaka has shed light on how malaria parasites evade immune defenses while paradoxically triggering immune responses. The study focuses on RIFIN proteins, surface molecules expressed on infected erythrocytes. These proteins can bind to killer immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, which play a crucial role in identifying and destroying infected cells. Notably, RIFINs were found to interact with both inhibitory KIRs, like KIR2DL1, suppressing NK cell activity, and activating receptors, such as KIR2DS1, which promote immune response. This dual functionality suggests that RIFINs serve as both a shield and a target for immune responses, depending on which receptor they bind. The research involved screening infected cells and identifying that multiple RIFIN variants can bind to KIR2DL1, leading to NK cell inhibition and allowing the parasite to survive. Interestingly, RIFINs capable of binding to the activating KIR2DS1 were also identified, which, rather than aiding immune evasion, may help immune cells recognize and attack the parasite. The widespread presence of these RIFINs across diverse malaria strains suggests they are key players in the disease's persistence and are promising targets for future therapies. Understanding the dual role of RIFIN proteins could pave the way for novel interventions, including vaccines that can block these interactions and enhance immune responses against malaria.

Source: [https://medicalxpress.com/news/2025-06-dual-function-proteins-clues-immune.html]