title: Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes.
abstract: Sequestration of parasitized erythrocytes and dysregulation of the coagulation and complement system are hallmarks of severe Plasmodium falciparum malaria. A link between these events emerged through the discovery that the parasite digestive vacuole (DV), which is released together with infective merozoites into the bloodstream, dually activates the intrinsic clotting and alternative complement pathway. Complement attack occurs exclusively on the membrane of the DVs, and the question followed whether DVs might be marked for uptake by polymorphonuclear granulocytes (PMNs). We report that DVs are indeed rapidly phagocytosed by PMNs after schizont rupture in active human serum. Uptake of malaria pigment requires an intact DV membrane and does not occur when the pigment is extracted from the organelle. Merozoites are not opsonized and escape phagocytosis in nonimmune serum. Antimalarial Abs mediate some uptake of the parasites, but to an extent that is not sufficient to markedly reduce reinvasion rates. Phagocytosis of DVs induces a vigorous respiratory burst that drives the cells into a state of functional exhaustion, blunting the production of reactive oxygen species (ROS) and microbicidal activity upon challenge with bacterial pathogens. Systemic overloading of PMNs with DVs may contribute to the enhanced susceptibility of patients with severe malaria toward invasive bacterial infections.
authors.affiliation: Department of Medical Microbiology and Hygiene, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Prasad
authors.initials: P
authors.lastname: Dasari
authors.forename: Karina
authors.initials: K
authors.lastname: Reiss
authors.forename: Klaus
authors.initials: K
authors.lastname: Lingelbach
authors.forename: Stefan
authors.initials: S
authors.lastname: Baumeister
authors.forename: Ralph
authors.initials: R
authors.lastname: Lucius
authors.forename: Rachanee
authors.initials: R
authors.lastname: Udomsangpetch
authors.forename: Sebastian Chakrit
authors.initials: SC
authors.lastname: Bhakdi
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D016923:Cell Death / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology / Q000473:pathology; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D052940:Merozoites / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000469:parasitology* / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D010963:Plasmodium falciparum / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species