Malarial hemozoin is a Nalp3 inflammasome activating danger signal.

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Version: Final published version
Serval ID
serval:BIB_D931E988C46C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Malarial hemozoin is a Nalp3 inflammasome activating danger signal.
Journal
PloS one
Author(s)
Dostert C., Guarda G., Romero J.F., Menu P., Gross O., Tardivel A., Suva M.L., Stehle J.C., Kopf M., Stamenkovic I., Corradin G., Tschopp J.
ISSN
1932-6203[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
4
Number
8
Pages
e6510
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: epublish
Abstract
BACKGROUND: Characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive Nalp3 inflammasome. Plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. Thus, we hypothesized that hemozoin could activate the Nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. METHODOLOGY/PRINCIPAL FINDINGS: We found that hemozoin acts as a proinflammatory danger signal that activates the Nalp3 inflammasome, causing the release of IL-1beta. Similar to other Nalp3-activating particles, hemozoin activity is blocked by inhibiting phagocytosis, K(+) efflux and NADPH oxidase. In vivo, intraperitoneal injection of hemozoin results in acute peritonitis, which is impaired in Nalp3-, caspase-1- and IL-1R-deficient mice. Likewise, the pathogenesis of cerebral malaria is dampened in Nalp3-deficient mice infected with Plasmodium berghei sporozoites, while parasitemia remains unchanged. SIGNIFICANCE/CONCLUSIONS: The potent pro-inflammatory effect of hemozoin through inflammasome activation may possibly be implicated in plasmodium-associated pathologies such as cerebral malaria.
Pubmed
Web of science
Open Access
Yes
Create date
31/08/2009 15:33
Last modification date
20/08/2019 15:58
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