title: Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome.
abstract: 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.
authors: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Thornik
authors: T
authors: Reimer
authors: Michael H
authors: MH
authors: Shaw
authors: Luigi
authors: L
authors: Franchi
authors: Cevayir
authors: C
authors: Coban
authors: Ken J
authors: KJ
authors: Ishii
authors: Shizuo
authors: S
authors: Akira
authors: Toshihiro
authors: T
authors: Horii
authors: Ana
authors: A
authors: Rodriguez
authors: Gabriel
authors: G
authors: Núñez
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology*; D002469:Cell Separation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D016779:Malaria, Cerebral / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010962:Plasmodium berghei; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012333:RNA, Messenger