Sticking for a Cause: The Falciparum Malaria Parasites Cytoadherence Paradigm

Abstract

After a successful invasion, malaria parasite Plasmodium falciparum extensively remodels the infected erythrocyte cellular architecture, conferring cytoadhesive properties to the infected erythrocytes. Cytoadherence plays a central role in the parasite's immune-escape mechanism, at the same time contributing to the pathogenesis of severe falciparum malaria. In this review, we discuss the cytoadhesive interactions between P. falciparum infected erythrocytes and various host cell types, and how these events are linked to malaria pathogenesis. We also highlight the limitations faced by studies attempting to correlate diversity in parasite ligands and host receptors with the development of severe malaria.

Malarial Related Myopathies: A Rhabdomyolysis Story

“…Glycosylphosphatidylinositol toxin of Plasmodium spp. directly increased several molecules, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression, all interfere with vascular endothelial cells and increased the level of leukocyte and induced cytoadherence via the enzyme tyrosine kinasedependent signal transduction [51,55]. Thus further more, it also activates vascular endothelial cells through other pathway, named the tyrosine kinase-mediated signal transduction.…”

“…This condition took place whenever the IRBC's losses its deformability properties due to the obligate intracellular parasite that inhabit and parasitize inner proportion of the cells; this condition preceed cytoadherence of IRBC'S to vascular cell wall [50]. Sequestration has been correlated with two condition, namely (1) mechanical obstruction of blood flow in small blood vessels due to certain condition (in this context, Malaria) and (2) rapid and systemic vascular endothelial cell activation, which may lead to its pathology [51].…”

“…Other important features that might contribute to and play an important roles in intravascular erythrocytes sequestration, e.g affinity/avidity of binding, tissue distribution of such this potentially fatal condition, polymorphisms of receptors and ligands and also their interactions, etc [48]. Microvasculature obstruction and endothelial activation are two important key point that will precede fatality to the patient [51,52].…”

Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic Labeling

“…The Maurer's clefts facilitate the transport of immunovariant adhesins for presentation on knob‐like protrusions at the erythrocyte plasma membrane (EPM) for cytoadherence to vascular endothelial cells, autoagglutination to other infected erythrocytes, and rosetting of infected with uninfected erythrocytes (Figure 1a; Figure S1b–e, Supporting Information). [ 7,13–16 ] These erythrocyte modifications mainly evolved to generate immune escape mechanisms of the parasites, but they can also contribute to the pathogenesis of severe or complicated malaria tropica, for example, by causing the blockage of the postcapillary venules. [ 16 ] It is therefore crucial to properly examine and understand the cell biology of the parasite to successfully target and hopefully eradicate the disease.…”

“…[ 7,13–16 ] These erythrocyte modifications mainly evolved to generate immune escape mechanisms of the parasites, but they can also contribute to the pathogenesis of severe or complicated malaria tropica, for example, by causing the blockage of the postcapillary venules. [ 16 ] It is therefore crucial to properly examine and understand the cell biology of the parasite to successfully target and hopefully eradicate the disease.…”