Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome

Eur J Immunol. 2010 Mar;40(3):764-9. doi: 10.1002/eji.200939996.


Cerebral malaria is the most severe complication of Plasmodium falciparum infection in humans and the pathogenesis is still unclear. Using the P. berghei ANKA infection model of mice, we investigated a potential involvement of Nlrp3 and the inflammasome in the pathogenesis of cerebral malaria. Nlrp3 mRNA expression was upregulated in brain endothelial cells after exposure to P. berghei ANKA. Although beta-hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release of IL-1beta in macrophages through Nlrp3, we did not obtain evidence for a role of IL-1beta in vivo. Nlrp3 knock-out mice displayed a delayed onset of cerebral malaria; however, mice deficient in caspase-1, the adaptor protein ASC or the IL-1 receptor succumbed as WT mice. These results indicate that the role of Nlrp3 in experimental cerebral malaria is independent of the inflammasome and the IL-1 receptor pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology*
  • Brain / microbiology
  • Brain / pathology
  • Carrier Proteins / immunology*
  • Cell Separation
  • Disease Models, Animal
  • Endothelium, Vascular / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Inflammation / immunology
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / immunology
  • Lymphocyte Activation
  • Malaria, Cerebral / immunology*
  • Malaria, Cerebral / metabolism
  • Malaria, Cerebral / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiprotein Complexes / immunology*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Plasmodium berghei
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology


  • Carrier Proteins
  • Interleukin-1beta
  • Multiprotein Complexes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • RNA, Messenger