Malarial hemozoin is a Nalp3 inflammasome activating danger signal

Catherine Dostert1, Greta Guarda, Jackeline F Romero

  • 1Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.

Plos One
|August 5, 2009
PubMed
Abstract

Insights

Malaria parasite byproduct, hemozoin, activates the Nalp3 inflammasome, a key inflammatory pathway. This activation may contribute to severe malaria pathologies like cerebral malaria.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Cell Biology

Background:

  • Malaria symptoms like fever and neurodegeneration are linked to hyperactive Nalp3 inflammasome.
  • Plasmodium parasites produce hemozoin from heme detoxification during hemoglobin breakdown in red blood cells.

Purpose of the Study:

  • To investigate if hemozoin activates the Nalp3 inflammasome.
  • To explore the role of hemozoin-induced inflammasome activation in malaria pathogenesis.

Main Methods:

  • In vitro experiments to assess hemozoin's effect on Nalp3 inflammasome activation.
  • In vivo studies using mouse models, including Nalp3-, caspase-1-, and IL-1R-deficient mice.
  • Analysis of peritonitis and cerebral malaria development after hemozoin administration or Plasmodium infection.

Main Results:

  • Hemozoin acts as a proinflammatory danger signal, activating the Nalp3 inflammasome and inducing IL-1beta release.
  • Hemozoin's inflammasome-activating properties are dependent on phagocytosis, K(+) efflux, and NADPH oxidase.
  • In vivo, hemozoin triggers acute peritonitis, which is reduced in deficient mice.
  • Nalp3 deficiency dampens cerebral malaria pathogenesis without affecting parasitemia.

Conclusions:

  • Hemozoin potently activates the Nalp3 inflammasome, suggesting its role in malaria-associated inflammation.
  • Inflammasome activation by hemozoin may contribute to severe complications like cerebral malaria.

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