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Alteration of the autophagie response by Leishmania major promastigotes

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Matte, Christine; Moradin, Neda et Descoteaux, Albert . Alteration of the autophagie response by Leishmania major promastigotes In: 12ième Symposium Annuel de Parasitologie Moléculaire du Québec, 28-29 mai 2012, INRS- Institut Armand-Frapper, Laval, Qc, Canada.

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Résumé

The protozoan parasite Leishmania causes a spectrum of diseases in humans, ranging from self-healing skin ulcers to life-threatening visceral infection. These parasites primarily infect macrophages and are renowned for their ability to sabotage host-cell signal transduction pathways. The Akt/mammalian Target Of Rapamycin (mTOR) axis plays a pivotai role in the regulation of multiple cellular processes, including protein synthesis, cytokine secretion, apoptosis, and autophagy. lt is therefore a major target of infectious pathogens. ln this study, we aimed to investigate the impact of L. major promastigotes on the Ak/mTOR axis and downstream autophagy-related events. Infection of bone marrow-derived macrophages with L. major promastigotes caused rapid, time-dependent degradation of key components of the Akt/mTOR signaling axis, including Akt, mTOR and the Tuberous Sclerosis Complex-2 (TSC-2). Disruption of this pathway by L. major was dependent on the GPI-anchored zinc-dependent metalloprotease GP63, an important virulence factor of this parasite. lnterestingly, recruitment of the autophagie marker LC3 to the parasitophorous vacuole of L. major promastîgotes was inhibited by GP63, possibly due to GP63-mediated cleavage of vesicle-associated membrane protein 8 (VAMPS). lndeed, absence of VAMPS resulted in inhibition of LC3 recruitment to phagosomes containing GP63-deficient parasites. This study highlights a novel pathogenic mechanism used by L. major to interfere with the autophagie response and will provide a better understanding of Leishmania pathogenesis. Supported by CIHR

Type de document: Document issu d'une conférence ou d'un atelier
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 05 juill. 2017 20:26
Dernière modification: 05 juill. 2017 20:26
URI: https://espace.inrs.ca/id/eprint/5687

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