Host cell remodeling by pathogens: the exomembrane system inPlasmodium-infected erythrocytes

Emma S Sherling,Christiaan Van Ooij,Alain Filloux

doi:10.1093/femsre/fuw016

Abstract

Malaria is caused by infection of erythrocytes by parasites of the genus Plasmodium. To survive inside erythrocytes, these parasites induce sweeping changes within the host cell, one of the most dramatic of which is the formation of multiple membranous compartments, collectively referred to as the exomembrane system. As an uninfected mammalian erythrocyte is devoid of internal membranes, the parasite must be the force and the source behind the formation of these compartments. Even though the first evidence of the presence these of internal compartments was obtained over a century ago, their functions remain mostly unclear, and in some cases completely unknown, and the mechanisms underlying their formation are still mysterious. In this review, we provide an overview of the different parts of the exomembrane system, describing the parasitophorous vacuole, the tubovesicular network, Maurer's clefts, the caveola-vesicle complex, J dots and other mobile compartments, and the small vesicles that have been observed in Plasmodium-infected cells. Finally, we combine the data into a simplified view of the exomembrane system and its relation to the alterations of the host erythrocyte.

Highlights

Soon after the discovery of the Plasmodium parasite in the late 1800s as an intracellular pathogen of erythrocytes that causes malaria (Laveran 1880), it became clear that the parasite induces sweeping changes within the host cell
We provide an overview of the different parts of the exomembrane system, describing the parasitophorous vacuole, the tubovesicular network, Maurer’s clefts, the caveola-vesicle complex, J dots and other mobile compartments, and the small vesicles that have been observed in Plasmodium-infected cells
This study showed that there was no appreciable decrease in erythrocyte surface area between uninfected erythrocytes and erythrocytes that had been invaded by one, two, three or even four parasites (Dluzewski et al 1995), leading to the conclusion that the parasitophorous vacuole membrane (PVM) must be derived of lipids from a source other than the erythrocyte (Fig. 2C) or that the erythrocyte membrane used for PVM formation is replenished by parasite-derived lipids (Fig. 2D)

Summary

Introduction

Soon after the discovery of the Plasmodium parasite in the late 1800s as an intracellular pathogen of erythrocytes that causes malaria (Laveran 1880), it became clear that the parasite induces sweeping changes within the host cell. Freezefracture (McLaren et al 1977) and immuno-EM (Atkinson et al 1988; Dluzewski et al 1989), as well as fluorescence microscopy (Ward, Miller and Dvorak 1993), have shown that the PVM surrounding P. falciparum and P. knowlesi parasites lacks all major erythrocyte membrane and cytoskeletal proteins, including spectrin, ankyrin and band 3.

Results

Conclusion