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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.

SUBMITTER: Franke-Fayard B 

PROVIDER: S-EPMC1183563 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature

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Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration.

Franke-Fayard Blandine B   Janse Chris J CJ   Cunha-Rodrigues Margarida M   Ramesar Jai J   Büscher Philippe P   Que Ivo I   Löwik Clemens C   Voshol Peter J PJ   den Boer Marion A M MA   van Duinen Sjoerd G SG   Febbraio Maria M   Mota Maria M MM   Waters Andrew P AP  

Proceedings of the National Academy of Sciences of the United States of America 20050728 32


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 mala  ...[more]

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