Journal Article

Murine Malaria Parasite Sequestration: CD36 Is the Major Receptor, but Cerebral Pathology Is Unlinked to Sequestration

Que, Ivo, Mota, Maria M., Cunha-Rodrigues, Margarida, Marion A. M. den Boer, Febbraio, Maria, Voshol, Peter J., Waters, Andrew P., van Duinen, Sjoerd G., Büscher, Philippe, Janse, Chris J., Ramesar, Jai, Franke-Fayard, Blandine, Löwik, Clemens, Griffin, Diane E.

2005

Overview

Sequestration of malaria-parasite-infected erythrocytes in the microvasculature of organs is thought to be a significant cause of pathology. Cerebral malaria (CM) is a major complication of Plasmodium falciparum infections, and PfEMP1-mediated sequestration of infected red blood cells has been considered to be the major feature leading to CM-related pathology. We report a system for the real-time in vivo imaging of sequestration using transgenic luciferase-expressing parasites of the rodent malaria parasite Plasmodium berghei. These studies revealed that: (i) as expected, lung tissue is a major site, but, unexpectedly, adipose tissue contributes significantly to sequestration, and (ii) the class II scavenger-receptor CD36 to which PfEMP1 can bind is also the major receptor for P. berghei sequestration, indicating a role for alternative parasite ligands, because orthologues of PfEMP1 are absent from rodent malaria parasites, and, importantly, (iii) cerebral complications still develop in the absence of CD36-mediated sequestration, dissociating parasite sequestration from CM-associated pathology. Real-time in vivo imaging of parasitic processes may be used to evaluate the molecular basis of pathology and develop strategies to prevent pathology.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adipose tissue / Adipose Tissue - parasitology / Adipose Tissue - pathology / Adipose tissues / Animals / Biological Sciences / Blood / Brain - parasitology / Brain - pathology / CD36 Antigens - metabolism / Circulatory system / Enzymes / Erythrocytes / Erythrocytes - parasitology / Gene Transfer Techniques / Green Fluorescent Proteins / Infections / Luciferases - metabolism / Lung - parasitology / Lung - pathology / Lungs / Malaria / Malaria, Cerebral - pathology / Malaria, Cerebral - physiopathology / Medical imaging / Mice / Microscopy, Fluorescence - methods / Parasites / Parasitism / Pathology / Plasmodium berghei / Plasmodium berghei - genetics / Plasmodium berghei - metabolism / Plasmodium falciparum / Protozoan Proteins - metabolism / Rodents / Schizonts / Spleen / Time Factors / Vector-borne diseases