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HIF-1α impairs monocyte’s effector function and induces M2 macrophage polarization during chronicLeishmania donovani infection

Hammami, Akil; Abidin, Belma Melda; Charpentier, Tania; Fabié, Aymeric; Heinonen, Krista M.; Stäger, Simona (2016). HIF-1α impairs monocyte’s effector function and induces M2 macrophage polarization during chronicLeishmania donovani infection In: International Congress of Immunology Immunotherapy: Harnessing the Power of the Immune System, 21-26 August 2016, Melbourne, Australia.

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Résumé

Leishmaniadonovani impairs the immune responseby 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 lowoxygen tension, is stabilized inall 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
Informations complémentaires: European Journal of Immunology 46(suppl 1):1049 abstract 2454
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 27 févr. 2019 17:21
Dernière modification: 18 mars 2019 18:54
URI: http://espace.inrs.ca/id/eprint/5836

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