Malaria, the red cell, and the endothelium

Area of Science:

• Immunology
• Pathology
• Vaccinology

Background:

• Plasmodium falciparum malaria involves infected erythrocytes adhering to vascular endothelium.
• Cerebral malaria pathology is linked to excessive infected cell adherence and microvessel occlusion by rosettes.
• Endothelial receptors like CD36 and ICAM-1 mediate this adherence.

Purpose of the Study:

• To investigate the mechanism of Plasmodium falciparum infected erythrocyte adherence to vascular endothelium.
• To identify the malarial protein responsible for mediating this adherence.
• To evaluate the potential of targeting this protein for malaria treatment and vaccine development.

Main Methods:

• In vitro binding assays were used to study interactions between infected erythrocytes and endothelial cells.
• Identification of endothelial cell receptors and the corresponding malarial erythrocyte protein.

Main Results:

• Erythrocytes infected with mature Plasmodium falciparum adhere to vascular endothelial cells.
• A large malarial protein, PfEMP1, on infected erythrocytes mediates adherence to endothelial receptors such as CD36 and thrombospondin.
• Infected cell rosettes can occlude cerebral blood flow.

Conclusions:

• PfEMP1 is the key malarial protein mediating infected erythrocyte adherence to vascular endothelium.
• Blocking PfEMP1-mediated adherence may reduce malaria pathology and enhance infected cell clearance.
• PfEMP1 is a promising target for a multicomponent asexual malaria vaccine.