Therefore, the parasites extract these lipids directly from the serum or from the membranes of the host ( 11), leading to an inwards flow of lipids, including cholesterol ( 12). Despite the high lipid demands, the parasites are not capable to synthesize fatty acids or cholesterol de novo ( 9, 10). In addition, if cholesterol, the only component known to be essential for microdomains/detergent-resistant membranes formation ( 7), is depleted from trophozoite-infected red cells, the parasite is expelled from the vacuole, suggesting that in the course of intracellular growth, cholesterol is essential to maintain infection ( 8). There is an enormous demand for lipids due to parasite growth inside the host cell and subsequent replication ( 5, 6). However, at the same time the parasite occupation within the RBC volume changes from initially 4 to 80% ( 4). In the subsequent schizont stage, the parasites nucleus divides several times giving rise to daughter merozoites that egress the infected RBC to enter a new replication cycle ( 2).ĭuring the development of the asexual parasite, the volume of the RBC increases slightly (by ~17%) while the parasite develops into the trophozoite stage ( 3). The merozoites quickly invade uninfected red blood cells (RBCs) where they differentiate into ring forms that further grow into trophozoites. The replication cycle starts with the release of merozoites into the blood stream. It is widely accepted that the asexual intraerythrocytic replication of the parasites during the blood stage causes clinical malaria with all the associated morbidity and mortality. Plasmodium spp., the infectious causative agent of malaria, have a complex life cycle, including a liver and a blood stage in the human host. Malaria is a life-threating disease that claims the lives of more than 400 000 people annually ( 1). Overall, by revealing the molecular events we establish here a pathogen-host interaction that involves host cell membrane remodeling that defines the susceptibility towards cytolytic molecules. ![]() Interestingly, not the cholesterol depletion but rather the simultaneous exposure of phosphatidylserine, a negatively charged phospholipid, triggers resistance of late stage parasitized red blood cells towards the eukaryotic pore forming protein perforin. We confirm that Plasmodium falciparum infection efficiently depletes the red blood cells of cholesterol, which renders the parasite surrounding membranes susceptible to lysis by prokaryotic membrane disrupting proteins, such as lymphocytic granulysin or the human cathelicidin LL-37. Here, we follow up on the molecular mechanisms of parasite growth inhibition by human pore-forming proteins. ![]() We recently found that γδ T cells control parasite growth using pore-forming proteins to deliver their cytotoxic proteases, the granzymes, into blood residing parasites. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. Malaria remains one of the most serious health problems in developing countries.
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