Fig. 5

Effect of hemozoin on macrophages and Plasmodium. A A large number of mononuclear macrophages that uptake hemozoin were observed in infected mice. B, C The macrophages sustain damage when they phagocytose significant amounts of hemozoin in vitro (C), compared with the normal group (B). D–F This schematic diagram illustrates that when schizonts release merozoites, host macrophages can ingest and eliminate the merozoites (E); however, after macrophages ingest hemozoin, they are unable to eliminate the merozoites owing to damage or death caused by the ingested hemozoin (F). G–I Effect of artemether on P. yoelii 17XNL. Compared with the parasites observed at 0 h post-artemether treatment, vacuoles appear in the cytoplasm of the parasites at 4–6 h post-treatment. In contrast, at 16–18 h post-treatment, the cells become disrupted, and hemozoin aggregates abnormally. J This schematic diagram illustrates the mechanism through which artemisinin induces abnormal aggregation of hemozoin. Malaria parasites ingest hemoglobin to release heme, which is then degraded to release iron for the parasite’s metabolic needs. Excess heme is sequestered as hemozoin, thereby maintaining a balance between heme, iron, and their utilization within the parasite. In the presence of artemisinin, it interacts with heme or hemozoin, resulting in abnormal aggregation and disrupting the established balance, ultimately leading to parasite death. K A substantial amount of hemozoin (indicated by black arrows) can be detected in gametocytes under light microscopy. L This schematic diagram raises the question of whether hemozoin, as a waste product, should be expelled by gametocytes before entering the mosquito; however, they actually transport hemozoin into the mosquito. Hz, hemozoin; Mz, merozoite. All scale bars indicate 5 μm