Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation

Malaria Journal

Mary Lopez-Perez¹  Lars Hviid²  Filip C. Castberg³  Michael F. Ofori⁴  William van der Puije⁵ 

[1] Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Centre for Medical Parasitology, Department of Infectious Diseases and Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark;Centre for Medical Parasitology, Department of Infectious Diseases and Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark;Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana;Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana;West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), College of Basic and Applied Sciences, University of Ghana, Legon, Ghana;Centre for Medical Parasitology, Department of Infectious Diseases and Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark;

关键词: α-Macroglobulin;    Ghana;    Malaria;    Non-specific IgM;    PfEMP1;    Plasmodium falciparum;    Rosetting;    Severe malaria;   

DOI  :  10.1186/s12936-020-03438-8

来源: Springer

【 摘 要 】

BackgroundThe pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2-macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here.MethodsChildren 1–12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients.ResultsClinical data from 108 children classified as UM (n = 54) and SM cases (n = 54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n = 14) and SM (n = 20) children were analysed. Most of the field isolates bound non-immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum.ConclusionsThe results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.

【 授权许可】

CC BY