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Title: Malarial anemia: digestive vacuole of Plasmodium falciparum mediates complement deposition on bystander cells to provoke hemophagocytosis
Authors: Prasad Dasari
Anja Fries
Sophia D. Heber
Abdulgabar Salama
Igor Wolfgang Blau
Klaus Lingelbach
Sebastian Chakrit Bhakdi
Rachanee Udomsangpetch
Michael Torzewski
Karina Reiss
Sucharit Bhakdi
Klinikum der Johannes-Gutenberg-Universitat und Fachbereich Medizin
Charité – Universitätsmedizin Berlin
Philipps-Universität Marburg
Mahidol University
Robert Bosch Krankenhaus Stuttgart
Christian-Albrechts-Universitat zu Kiel
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Jan-2014
Citation: Medical Microbiology and Immunology. Vol.203, No.6 (2014), 383-393
Abstract: © 2014, Springer-Verlag Berlin Heidelberg. The digestive vacuole (DV) of Plasmodium falciparum, which is released into the bloodstream upon rupture of each parasitized red blood cell (RBC), was recently discovered to activate the alternative complement pathway. In the present work, we show that C3- and C5-convertases assembling on the parasitic organelle are able to provoke deposition of activated C3 and C5b-9 on non-infected bystander erythrocytes. Direct contact of DVs with cells is mandatory for the effect, and bystander complement deposition occurs focally, possibly at the sites of contact. Complement opsonization promotes protracted erythrophagocytosis by human macrophages, an effect that is magnified when ring-stage infected RBCs with reduced CD55 and CD59, or paroxysmal nocturnal hemoglobinuria (PNH)-RBCs lacking these complement inhibitors are employed as targets. Bystander attack can also directly induce lysis of PNH-RBCs. Direct evidence for complement activation and bystander attack mediated by DVs was obtained through immunohistochemical analyses of brain paraffin sections from autopsies of patients who had died of cerebral malaria. C3d and the assembled C5b-9 complex could be detected in all sections, colocalizing with and often extending locally beyond massive accumulations of DVs that were identified under polarized light. This is the first demonstration that a complement-activating particle can mediate opsonization of bystander cells to promote their antibody-independent phagocytosis. The phenomenon may act in concert with other pathomechanisms to promote the development of anemia in patients with severe malaria.
ISSN: 14321831
Appears in Collections:Scopus 2011-2015

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