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Disruption of Akt downstream events by Leishmania major promastigotes

Matte, Christine; Descoteaux, Albert . Disruption of Akt downstream events by Leishmania major promastigotes In: 11ième Symposium Annuel de Parasitologie Moléculaire du Québec, 7-8 juin 2011, Université McGill.

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Résumé

Signaling through the Akt/mammalian target of rapamycin (mTOR) pathway plays a pivotal role in the regulation of multiple cellular processes, including protein synthesis, cytokine secretion, autophagy and apoptosis. It is therefore a major target of microbial infections and tumors. Protozoa of the Leishmania genus cause a wide spectrum of diseases in humans, termed leishmaniases, with clinical manifestations ranging from self-healing skin ulcers to lifethreatening visceral disease. These parasites primarily infect macrophages and are renowned for their ability to sabotage host-cell signal transduction pathways. Here, we report that infection of Balb/c bone marrow-derived macrophages (BMDM) with the promastigote stage of Leishmania major causes rapid, time-dependent degradation of key components of the Akt/mTOR axis, including Akt, mTOR and the tuberous sclerosis complex-2 (TSC-2). Results show that disruption of the Akt/mTOR pathway by L. major is dependent on the surface metalloprotease gp63, an important virulence factor of the parasite, and appears to be species- and strain-specific. Analysis of IL-12 secretion by infected BMDM indicated that L. major promastigotes promote production of this cytokine, although the precise mechanism underlying this effect has yet to be identified. The impact of L. major onthe autophagic system and on apoptosis is currently being investigated. These studies highlight a novel mechanismby which L. major interferes with macrophage functions and responses and will provide a better understanding of Leishmania pathogenesis.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Présentation par affiche
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 03 mai 2018 15:34
Dernière modification: 03 mai 2018 15:34
URI: http://espace.inrs.ca/id/eprint/7110

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