Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage.
The destruction of erythrocytes and defects in erythropoiesis are among the most frequently observed causes of morbidity in severe Plasmodium falciparum malaria. The molecular mechanisms involved remain unclear, despite extensive investigation. We show here, for the first time, that tagging with the parasite rhoptry protein ring surface protein 2 (RSP2) is not restricted to the surfaces of normal erythrocytes, as previously reported, but that it extends to erythroid precursor cells in the bone marrow of anemic malaria patients. Monoclonal mouse antibodies and human sera from patients with severe anemia, reacting with RSP2-tagged erythrocytes, induced cell destruction by phagocytosis and complement activation in vitro. Our observations reveal a new parasite mechanism implicated in the destruction of normal erythrocytes and probably dyserythropoiesis in malaria patients. These data suggest that the tagging of host cells with RSP2 may trigger anemia in falciparum malaria.
Layez
Corinne
C
Unité de Parasitologie Expérimentale, URA Institut Pasteur/Univ. Med. EA3282, IFR48, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
Nogueira
Paulo
P
Combes
Valery
V
Costa
Fabio T M
FT
Juhan-Vague
Irène
I
da Silva
Luiz H Pereira
LH
Gysin
Jürg
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D015672:Erythroid Precursor Cells / Q000276:immunology* / Q000469:parasitology; D004920:Erythropoiesis / Q000276:immunology*; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015800:Protozoan Proteins; C073168:rhoptry-associated antigen-2, Plasmodium