Hammami, Akil; Abidin, Belma Melda; Charpentier, Tania; Fabié, Aymeric; Heinonen, Krista M. et Stäger, Simona . HIF-1α impairs monocyte effector function and induces M2 macrophage polarization during chronic Leishmania donovani infection In: 16e symposium annuel de parasitologie moléculaire du Québec, 6-7 juin 2016, Université McGill, Montréal, QC.
Ce document n'est pas hébergé sur EspaceINRS.Résumé
Leishmania donovani impairs the immune response by triggering a hypoxic micro-environment that facilitates the establishment of a chronic infection. Under this condition, HIF-1α, the master regulator of the response to low oxygen tension, is stabilized in all cell populations. The effect of hypoxia on the immune response to Leishmania has not yet been investigated. Particularly, the role of HIF-1α in macrophage and monocyte function during chronic visceral leishmaniasis remains unknown. Here, we investigate the role of HIF-1α in inflammatory monocyte and dendritic cell functions, and in the modulation of macrophage polarization during chronic L. donovani infection. To this end, we generated CD11c-specific HIF-1α knock-out mice that were then infected with L. donovani. Our data demonstrate that HIF-1α limits inflammatory monocyte recruitment to the spleen and induces M2 macrophage polarization in response to extracellular lactate. The ablation of HIF-1α in CD11c+ cells resulted in decreased intracellular lactate concentrations, lower expression of M2 macrophage markers, greater expansion and effector capacity of monocytes, and enhanced IFNϒ+ production by CD4+ T cells. Moreover, mice with a targeted depletion of HIF-1α in CD11c+ cells had a significantly lower splenic parasite burden, suggesting that induction of HIF-1α in CD11c+ cells may represent a key factor adopted by Leishmania parasites to establish persistent infections.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 01 mai 2018 20:23 |
| Dernière modification: | 18 mars 2019 18:55 |
| URI: | https://espace.inrs.ca/id/eprint/7072 |
Gestion Actions (Identification requise)
 |
Modifier la notice |