Rosiglitazone Modulates the Innate Immune Response toPlasmodium falciparumInfection and Improves Outcome in Experimental Cerebral Malaria
Open Access
- 15 May 2009
- journal article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 199 (10), 1536-1545
- https://doi.org/10.1086/598222
Abstract
For severe malarial syndromes such as cerebral malaria, adverse clinical outcomes are often mediated by the immune system rather than caused by the parasite directly. However, few therapeutic agents have been developed to modulate the host’s immunopathological responses to infection. Here, we report that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone modulated the host response to malaria by enhancing phagocytic clearance of malaria-parasitized erythrocytes and by decreasing inflammatory responses to infection via inhibition of Plasmodium falciparum glycosylphosphatidylinositol-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor–κB (NF-κB) signaling pathways. We found that, in the Plasmodium berghei strain ANKA experimental model of cerebral malaria, rosiglitazone modified the inflammatory response to malarial infection and improved the survival rate even when treatment was initiated as late as day 5 after infection. Furthermore, rosiglitazone reduced the parasitemia in a CD36-dependent manner in the Plasmodium chabaudi chabaudi hyperparasitemia model. These data suggest that PPARγ agonists represent a novel class of host immunomodulatory drugs that may be useful for treatment of severe malaria syndromesKeywords
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