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Leishmania inhibits antigen crosspresentation by direct cleavage of the SNARE VAMPS

Moradin, Neda; Matheoud, Diana; Hong, Wan Jin; Desjardins, Michel; Descoteaux, Albert . Leishmania inhibits antigen crosspresentation by direct cleavage of the SNARE VAMPS 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

Phagosomes play a key role in immunity by killing microbes and processing their antigens for T cell activation. Sorne intracellular pathogens such as Leishmania inhibit these steps and prevent phagosome maturation through different mechanisms. ln the present study, we investigated the impact of infection on SNAREs (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) proteins involved in the trafficking ta and from the phagosome. We discovered that upon infection, VAMPS, VAMP3, SNAP23, and syntaxin-4 were cleaved by GPI-anchored zinc metalloprotease GP63. Using a L. major gp63-KO mutant, we showed that this parasite protease is responsible for the cleavage of VAMPS and other SNAREs in infected macrophages. We also found that Leishmania promastigotes inhibit antigen crosspresentation in a GP63-dependent manner. Using cells from VAMPS-deficient mice, we confirmed that this SNARE protein is required for antigen crosspresentation. Also, the phagosomal exclusion of Sec22b, one of the regulators in phagosome maturation and antigen cross presentation, was observed upon infection with L. major WT and gp63-KO add-back. Thus, we uncovered the existence of a novel mechanism used by Leishmania promastigotes to evade recognition by the immune system, whereby the parasites impair crosspresentation by degrading key regulators of vesicular trafficking.

Type de document: (NON SPÉCIFIÉ)
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 05 juill. 2017 20:25
Dernière modification: 05 juill. 2017 20:25
URI: http://espace.inrs.ca/id/eprint/5685

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