Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome.
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.
Reimer
Thornik
T
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Shaw
Michael H
MH
Franchi
Luigi
L
Coban
Cevayir
C
Ishii
Ken J
KJ
Akira
Shizuo
S
Horii
Toshihiro
T
Rodriguez
Ana
A
Núñez
Gabriel
G
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
D002352:Carrier Proteins; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012333:RNA, Messenger