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The host cell secretory pathway mediates the export of Leishmania virulence factors out of the parasitophorous vacuole

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Arango Duque, Guillermo; Jardim, Armando; Gagnon, Étienne; Fukuda, Mitsunori; Descoteaux, Albert (2019). The host cell secretory pathway mediates the export of Leishmania virulence factors out of the parasitophorous vacuole PLoS Pathogens , vol. 15 , nº 7:e1007982. p. 1-25. DOI: 10.1371/journal.ppat.1007982..

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Résumé

To colonize phagocytes, Leishmania subverts microbicidal processes through components of its surface coat that include lipophosphoglycan and the GP63 metalloprotease. How these virulence glycoconjugates are shed, exit the parasitophorous vacuole (PV), and traffic within host cells is poorly understood. Here, we show that lipophosphoglycan and GP63 are released from the parasite surface following phagocytosis and redistribute to the endoplasmic reticulum (ER) of macrophages. Pharmacological disruption of the trafficking between the ER and the Golgi hindered the exit of these molecules from the PV and dampened the cleavage of host proteins by GP63. Silencing by RNA interference of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptors Sec22b and syntaxin-5, which regulate ER-Golgi trafficking, identified these host proteins as components of the machinery that mediates the spreading of Leishmania effectors within host cells. Our findings unveil a mechanism whereby a vacuolar pathogen takes advantage of the host cell's secretory pathway to promote egress of virulence factors beyond the PV.

Type de document: Article
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 20 nov. 2019 16:01
Dernière modification: 20 nov. 2019 16:01
URI: http://espace.inrs.ca/id/eprint/8642

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