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Leishmania donovani metacyclic promastigotes colonize inflammatory monocytes by impairing phagosome function

Matte, Christine et Descoteaux, Albert . Leishmania donovani metacyclic promastigotes colonize inflammatory monocytes by impairing phagosome function In: Annual Meeting of the American-Association-of-Immunologists - Immunology 2020, 8-12 July 2020, Honolulu, HI.

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Résumé

Protozoan parasites of the Leishmania genus are the etiological agents of leishmaniasis, a debilitating disease with a wide spectrum of clinical symptoms ranging from self-healing ulcers to life-threatening visceral pathologies. These vacuolar pathogens are transmitted to mammalian hosts as metacyclic promastigotes by the bite of an infected sandfly. Parasites are then internalized by various phagocyte populations such as inflammatory monocytes. The nature of Leishmania-monocyte interactions over the course of infection and the specific role of these cells in pathogenesis are still unclear. Here, we aimed to investigate the impact of Leishmania donovani metacyclic promastigotes on inflammatory monocyte antimicrobial responses. Our results first show that these cells are highly permissive to L. donovani infection, while bacteria are rapidly eliminated. Upon internalization, L. donovani promastigotes inhibit phagosome acidification, as detected by confocal microscopy using the acidotropic probe LysoTracker. Furthermore, these parasites inhibit NOX2 assembly at the parasitophorous vacuole. Indeed, we found that the membrane-bound subunit gp91phox and the cytosolic subunit p47phox are excluded from the PV membrane. As a result, L. donovani metacyclic promastigotes prevent the production of reactive oxygen species within the PV, as detected using NitroBlue Tetrazolium. Permissiveness of inflammatory monocytes to L. donovani may thus be related to the ability of this parasite to impair the microbicidal properties of phagosomes. The virulence factors involved in these processes are currently being investigated.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique P506 Journal of Immunology 204 (suppl 1) 149.19 https://www.jimmunol.org/content/204/1_Supplement/149.19
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 14 juill. 2021 15:57
Dernière modification: 14 juill. 2021 15:57
URI: https://espace.inrs.ca/id/eprint/11817

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