Serum Lipoproteins Promote Efficient Presentation of the Malaria Virulence Protein PfEMP1 at the Erythrocyte Surface

Author:

Frankland Sarah12,Elliott Salenna R.3,Yosaatmadja Francisca3,Beeson James G.4,Rogerson Stephen J.3,Adisa Akinola1,Tilley Leann15

Affiliation:

1. Department of Biochemistry

2. Cooperative Research Centre for Vaccine Technology

3. Department of Medicine, University of Melbourne, Post Office Royal Melbourne Hospital, Parkville 3050, Australia

4. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3050 VIC, Australia

5. Centre of Excellence for Coherent X-ray Science, La Trobe University, Melbourne 3086, Australia

Abstract

ABSTRACT The virulence of the malaria parasite Plasmodium falciparum is related to its ability to express a family of adhesive proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1) at the infected red blood cell surface. The mechanism for the transport and delivery of these adhesins to the erythrocyte membrane is only poorly understood. In this work, we have used specific immune reagents in a flow cytometric assay to monitor the effects of serum components on the surface presentation of PfEMP1. We show that efficient presentation of the A4 and VAR2CSA variants of PfEMP1 is dependent on the presence of serum in the bathing medium during parasite maturation. Lipid-loaded albumin supports parasite growth but allows much less efficient presentation of PfEMP1 at the red blood cell surface. Analysis of the serum components reveals that lipoproteins, especially those of the low-density lipoprotein fraction, promote PfEMP1 presentation. Cytoadhesion of infected erythrocytes to the host cell receptors CD36 and ICAM-1 is also decreased in infected erythrocytes cultured in the absence of serum. The defect appears to be in the transfer of PfEMP1 from parasite-derived structures known as the Maurer's clefts to the erythrocyte membrane or in surface conformation rather than a down-regulation or switching of particular PfEMP1 variants.

Publisher

American Society for Microbiology

Subject

Molecular Biology,General Medicine,Microbiology

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