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NLRP3 inflammasome in malaria: role of hemozoin-induced signaling on inflammasome activation

Shio, Marina Tiemi; Eisenbarth, Stephanie C.; Savaria, Myriam; Vinet, Adrien F.; Bellemare, Marie-Josée; Harder, Kenneth W.; Sutterwala, Fayyaz S.; Bohle, D. Scott; Descoteaux, Albert; Flavell, Richard A.; Olivier, Martin . NLRP3 inflammasome in malaria: role of hemozoin-induced signaling on inflammasome activation In: 9e symposium annuel de parasitologie moléculaire du Québec, 18-19 juin 2009, Université McGill.

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Résumé

The intraerythrocytic Plasmodium parasite - the causative agent of Malaria - produces an inorganic crystal called hemozoin (Hz) during heme detoxification process, which is released into the circulation during erythrocyte lysis. Hz is rapidly ingested by phagocytes and induces the production of several pro-inflammatory mediators such as interleukin-1β (IL-1β). However, the mechanism regulating Hz recognition and IL-1β maturation has not been identified. Here, we show that Hz induces IL-1β production dependent on NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome, ASC and caspase-1, but not NLRC4 (NLR containing CARD domain). Furthermore, we observe that the absence of NLRP3 or IL-1β augmented mice survival to malaria caused by P. chabaudi AS. We further demonstrate, using pharmacological and genetic intervention, that the tyrosine kinases Syk and Lyn play a critical role in this inflammasome activation. These findings not only identify one way by which the immune system is alerted to malaria infection but also are the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLPR3 inflammasome and its role in the control the malaria progression. This work was supported by an operating grant of CIHR to MO. CNPq/Brazil and Research Institute of the McGill University Health Centre fellowship to MTS.

Type de document: Document issu d'une conférence ou d'un atelier
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 02 mai 2018 20:51
Dernière modification: 02 mai 2018 20:51
URI: http://espace.inrs.ca/id/eprint/7104

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