Da Mota, Maria Manuel Dias; (1998) Sequestration and the infected-erythrocyte surface in plasmodium chabaudi malaria infection. Doctoral thesis (Ph.D.), University College London.

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Abstract

Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1 coded by a gene family - var) is involved in sequestration, antigenic variation and acquired immunity. Much of this information has been gained from the study of parasites maintained in vitro. The major objective of the current work has been to characterize a model where these phenomena can be studied in vivo in a context of a dynamic host-parasite relationship. P. chabaudi chabaudi AS infected erythrocytes have been analysed in sequestration and adhesion assays and we have studied the antibody response in mice to parasite-derived erythrocyte surface antigens. Results demonstrate that P. c. chabaudi AS sequesters primarily in the liver and spleen of these mice and the molecular basis for this phenomena is very similar to that seen with P. falciparum. Antibody response during the acute phase of infection is directed against parasite-line specific erythrocyte surface antigens promoting the phagocytosis of homologous infected-erythrocytes. Therefore, this model presents many similarities to P. falciparum infection of humans. As with P. falciparum in humans, sequestration and antigenic variation appear to be intimately linked in P. c. chabaudi AS infections indicating that the protein responsible for both phenomena may be a homologue of PfEMP-1. In an attempt to identify the P. c. chabaudi AS homologue of Pfvar, a gene family was identified that is expressed during the parasite erythrocytic life cycle. The deduced protein sequence contains a cysteine rich-domain. Antibodies raised against it recognize a protein with similar size to PfEMP-1 that is partially insoluble in Triton X-100 and is localized around some mature parasites. These results are discussed in the context of validating a rodent model to study sequestration, antigenic variation and acquired immunity in vivo.

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