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Nrf2, a PPAR? alternative pathway to promote CD36 expression on inflammatory macrophages: implication for malaria.


ABSTRACT: CD36 is the major receptor mediating nonopsonic phagocytosis of Plasmodium falciparum-parasitized erythrocytes by macrophages. Its expression on macrophages is mainly controlled by the nuclear receptor PPAR?. Here, we demonstrate that inflammatory processes negatively regulate CD36 expression on human and murine macrophages, and hence decrease Plasmodium clearance directly favoring the worsening of malaria infection. This CD36 downregulation in inflammatory conditions is associated with a failure in the expression and activation of PPAR?. Interestingly, using siRNA mediating knock down of Nrf2 in macrophages or Nrf2- and PPAR?-deficient macrophages, we establish that in inflammatory conditions, the Nrf2 transcription factor controls CD36 expression independently of PPAR?. In these conditions, Nrf2 activators, but not PPAR? ligands, enhance CD36 expression and CD36-mediated Plasmodium phagocytosis. These results were confirmed in human macrophages and in vivo where only Nrf2 activators improve the outcome of severe malaria. Collectively, this report highlights that the Nrf2 transcription factor could be an alternative target to PPAR? in the control of severe malaria through parasite clearance.

SUBMITTER: Olagnier D 

PROVIDER: S-EPMC3174257 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Nrf2, a PPARγ alternative pathway to promote CD36 expression on inflammatory macrophages: implication for malaria.

Olagnier David D   Lavergne Rose-Anne RA   Meunier Etienne E   Lefèvre Lise L   Dardenne Christophe C   Aubouy Agnès A   Benoit-Vical Françoise F   Ryffel Bernhard B   Coste Agnès A   Berry Antoine A   Pipy Bernard B  

PLoS pathogens 20110915 9


CD36 is the major receptor mediating nonopsonic phagocytosis of Plasmodium falciparum-parasitized erythrocytes by macrophages. Its expression on macrophages is mainly controlled by the nuclear receptor PPARγ. Here, we demonstrate that inflammatory processes negatively regulate CD36 expression on human and murine macrophages, and hence decrease Plasmodium clearance directly favoring the worsening of malaria infection. This CD36 downregulation in inflammatory conditions is associated with a failur  ...[more]

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