1. Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome
- Author
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Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA ; Paul H. Dekruif Professor of Pathology, University of Michigan Medical School, 1500 E. Medical Center Dr, 4215 CCGC, Ann Arbor, MI 48109, USA Fax: +1-734-647-9654, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan ; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Medical Parasitology, New York University School of Medicine, New York, NY, USA, Reimer, Thornik, Shaw, Michael H., Franchi, Luigi, Coban, Cevayir, Ishii, Ken J., Akira, Shizuo, Horii, Toshihiro, Rodriguez, Ana, N????ez, Gabriel, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA ; Paul H. Dekruif Professor of Pathology, University of Michigan Medical School, 1500 E. Medical Center Dr, 4215 CCGC, Ann Arbor, MI 48109, USA Fax: +1-734-647-9654, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan, Laboratory of Host Defense, Immunology Frontier Research Center, World Premier Immunology Institute, Osaka University, Osaka, Japan ; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan, Department of Medical Parasitology, New York University School of Medicine, New York, NY, USA, Reimer, Thornik, Shaw, Michael H., Franchi, Luigi, Coban, Cevayir, Ishii, Ken J., Akira, Shizuo, Horii, Toshihiro, Rodriguez, Ana, and N????ez, Gabriel
- 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 ??-hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release of IL-1?? in macrophages through Nlrp3, we did not obtain evidence for a role of IL-1?? 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.
- Published
- 2010