Rosiglitazone modulates the innate immune response to plasmodium falciparum infection and improves outcome in experimental cerebral malaria

Lena Serghides, Samir N. Patel, Kodjo Ayi, Ziyue Lu, Channe Gowda, W. Conrad Liles, Kevin C. Kain

Research output: Contribution to journalArticle

51 Citations (Scopus)

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-kB (NF-kB) signaling pathways. We found that, in the Plasmodium berghei strainANKAexperimental 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 syndromes.

Original languageEnglish (US)
Pages (from-to)1536-1545
Number of pages10
JournalJournal of Infectious Diseases
Volume199
Issue number10
DOIs
StatePublished - May 15 2009

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rosiglitazone
Cerebral Malaria
Plasmodium falciparum
Innate Immunity
Malaria
Peroxisome Proliferator-Activated Receptors
Infection
Plasmodium chabaudi
Plasmodium berghei
Glycosylphosphatidylinositols
Parasitemia
Mitogen-Activated Protein Kinases
Immune System
Parasites
Therapeutics
Erythrocytes
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Serghides, Lena ; Patel, Samir N. ; Ayi, Kodjo ; Lu, Ziyue ; Gowda, Channe ; Liles, W. Conrad ; Kain, Kevin C. / Rosiglitazone modulates the innate immune response to plasmodium falciparum infection and improves outcome in experimental cerebral malaria. In: Journal of Infectious Diseases. 2009 ; Vol. 199, No. 10. pp. 1536-1545.
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Rosiglitazone modulates the innate immune response to plasmodium falciparum infection and improves outcome in experimental cerebral malaria. / Serghides, Lena; Patel, Samir N.; Ayi, Kodjo; Lu, Ziyue; Gowda, Channe; Liles, W. Conrad; Kain, Kevin C.

In: Journal of Infectious Diseases, Vol. 199, No. 10, 15.05.2009, p. 1536-1545.

Research output: Contribution to journalArticle

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