Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies
Kristina E.M. Persson, … , Kevin Marsh, James G. Beeson
Kristina E.M. Persson, … , Kevin Marsh, James G. Beeson
Published December 6, 2007
Citation Information: J Clin Invest. 2008;118(1):342-351. https://doi.org/10.1172/JCI32138.
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Research Article Infectious disease

Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies

Abstract

Antibodies that inhibit Plasmodium falciparum invasion of erythrocytes are believed to be an important component of immunity against malaria. During blood-stage infection, P. falciparum can use different pathways for erythrocyte invasion by varying the expression and/or utilization of members of 2 invasion ligand families: the erythrocyte-binding antigens (EBAs) and reticulocyte-binding homologs (PfRhs). Invasion pathways can be broadly classified into 2 groups based on the use of sialic acid (SA) on the erythrocyte surface by parasite ligands. We found that inhibitory antibodies are acquired by malaria-exposed Kenyan children and adults against ligands of SA-dependent and SA-independent invasion pathways, and the ability of antibodies to inhibit erythrocyte invasion depended on the pathway used by P. falciparum isolates. Differential inhibition of P. falciparum lines that varied in their use of specific EBA and PfRh proteins pointed to these ligand families as major targets of inhibitory antibodies. Antibodies against recombinant EBA and PfRh proteins were acquired in an age-associated manner, and inhibitory antibodies against EBA175 appeared prominent among some individuals. These findings suggest that variation in invasion phenotype might have evolved as a mechanism that facilitates immune evasion by P. falciparum and that a broad inhibitory response against multiple ligands may be required for effective immunity.

Authors

Kristina E.M. Persson, Fiona J. McCallum, Linda Reiling, Nicole A. Lister, Janine Stubbs, Alan F. Cowman, Kevin Marsh, James G. Beeson

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Figure 2

The phenotypes and invasion of the different P. falciparum lines used.

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The phenotypes and invasion of the different P. falciparum lines used. ...
(A) Demonstration of phenotypic differences in erythrocyte invasion by comparing the effect of neuraminidase or chymotrypsin treatment of erythrocytes on the invasion of different P. falciparum lines. Results are expressed as percentage invasion relative to erythrocytes treated with control (buffer); values represent mean ± SEM from 4 different experiments. Chym, chymotrypsin-treated erythrocytes; Neur, neuraminidase-treated erythrocytes. (B) Multiplication rates for different P. falciparum lines, cultured in normal erythrocytes. The multiplication rate represents the fold increase in parasitemia over 2 parasite life cycles for each parasite line. All samples were tested in duplicate; values represent mean ± range from 2 different experiments. (C) Inhibition of invasion of P. falciparum lines by rabbit antibodies against MSP119. All samples were tested in duplicate; values represent mean ± range from 2 different experiments. Results are expressed as the percent of invasion observed with control samples.