Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration
Abstract
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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2005
- DOI:
- 10.1073/pnas.0503386102
- Bibcode:
- 2005PNAS..10211468F
- Keywords:
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- imaging;
- Plasmodium;
- P. berghei;
- luciferase;
- real-time in vivo imaging;
- Medical Sciences, Biological Sciences