Dépôt numérique

Alteration of macrophage membrane fusion regulators during infection with Leishmania promastigotes

Moradin, Neda; Matheoud, Diana; Fukuda, Mitsunori; Desjardins, Michel et Descoteaux, Albert . Alteration of macrophage membrane fusion regulators during infection with Leishmania promastigotes In: 11ième Symposium Annuel de Parasitologie Moléculaire du Québec, 7-8 juin 2011, Université McGill.

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Some pathogens like Leishmania promastigotes inhibit phagosome maturation. This inhibition is mediated by the different virulence factors such the promastigote surface glycolipid lipophosphoglycan, which causes exclusion of Synaptotagmin V from the phagosome membrane. As a consequence, promatigotes establish infection in a phagosome from which the vesicular proton-ATPase is excluded and which fails to acidify. Synaptotagmins constitute a large family of membrane-trafficking proteins which are in close interaction with SNAREs (soluble Nethylmaleimide-sensitive-factor attachment protein receptor) proteins. To investigate the impact of some key SNAREs on the control of Leishmania, we infected macrophages with different species and strains of Leishmania for different periods and we discovered that upon infection, there was degradation of VAMP8, VAMP3 and Syntaxin4 by some species and strains of Leishmania. This degradation is strictly dependent on the presence of the Leishmania surface zinc-metalloprotease gp63. In fact, using a gp63-/- mutant, we observed no degradation of those SNAREs. Also, by using macrophages and dendritic cells from VAMP8 knock-out mice, we showed that VAMP8 is essential for the cross presentation pathway which we confirmed the same results after infection of wild-type macrophages with Leishmania. Taken together, by discovering new virulence mechanism of Leishmania, there is a chance to target some components through invading pathway and also, prevention of phagosome maturation to control this parasitic disease in a near future.

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: 03 mai 2018 15:39
Dernière modification: 03 mai 2018 15:39
URI: https://espace.inrs.ca/id/eprint/7111

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