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Olagnier D., Lavergne R. A., Meunier E., Lefevre L., Dardenne C., Aubouy Agnès, Benoit-Vical F., Ryffel B., Coste A., Berry A., Pipy B. Nrf2, a PPAR gamma alternative pathway to promote CD36 expression on inflammatory macrophages : implication for malaria. Plos Pathogens, 2011, 7 (9), p. e1002254. ISSN 1553-7366
Document en accès réservé (Intranet IRD)
doi:10.1371/journal.ppat.1002254
| Titre | Nrf2, a PPAR gamma alternative pathway to promote CD36 expression on inflammatory macrophages : implication for malaria |
| Année de publication | 2011 |
| Type de document | Article référencé dans le Web of Science WOS:000295409000054 |
| Auteurs | Olagnier D., Lavergne R. A., Meunier E., Lefevre L., Dardenne C., Aubouy Agnès, Benoit-Vical F., Ryffel B., Coste A., Berry A., Pipy B. |
| Source | Plos Pathogens, 2011, 7 (9), p. e1002254. p. e1002254 ISSN 1553-7366 |
| Résumé | 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 gamma. 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 gamma. Interestingly, using siRNA mediating knock down of Nrf2 in macrophages or Nrf2- and PPAR gamma-deficient macrophages, we establish that in inflammatory conditions, the Nrf2 transcription factor controls CD36 expression independently of PPAR gamma. In these conditions, Nrf2 activators, but not PPAR gamma 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 gamma in the control of severe malaria through parasite clearance. |
| Plan de classement | 052 |
| Localisation | Fonds IRD [F B010053886] |
| Identifiant IRD | fdi:010053886 |
| Lien permanent | http://www.documentation.ird.fr/hor/fdi:010053886 |
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