Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction

Lucie Paloque (1, 2) , Teresa Pérez-Berezo (3) , Anne Abot (3) , Jessica Dalloux-Chioccioli (4) , Sandra Bourgeade-Delmas (2) , Pauline Le Faouder (4) , Julien Pujo (3) , Marie-Ange Teste (5) , Jean Marie François (5) , Nils Helge Schebb (6) , Malwina Mainka (6) , Corinne Rolland (3) , Catherine Blanpied (3) , Gilles Dietrich (3) , Justine Bertrand-Michel (4) , Céline Deraison (3) , Alexis Valentin (2) , Nicolas Cénac (3)

1 LCC - Laboratoire de chimie de coordination
2 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
3 IRSD - Institut de Recherche en Santé Digestive
4 MetaToul Lipidomics
5 LISBP - Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés
6 University of Wuppertal

Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophage functions. Among these strategies, Leishmania as a source of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of polyunsaturated fatty acid metabolites by infective and noninfective stages of Leishmania and further explored the role of these metabolites in macrophage polarization. The concentration of docosahexaenoic acid metabolites, precursors of proresolving lipid mediators, was increased in the infective stage of the parasite compared with the noninfective stage, and cytochrome P450-like proteins were shown to be implicated in the biosynthesis of these metabolites. The treatment of macrophages with lipids extracted from the infective forms of the parasite led to M2 macrophage polarization and blocked the differentiation into the M1 phenotype induced by IFN-γ. In conclusion, Leishmania polyunsaturated fatty acid metabolites, produced by cytochrome P450-like protein activity, are implicated in parasite/host interactions by promoting the polarization of macrophages into a proresolving M2 phenotype.

Mots clés: Cytochrome P450; Infection; Macrophages; ω-3; Metabolism; Arachidonic acid; Eicosanoids

Domaines: Chimie de coordination

Lucie Paloque, Teresa Pérez-Berezo, Anne Abot, Jessica Dalloux-Chioccioli, Sandra Bourgeade-Delmas, et al.. Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction. Journal of Lipid Research, 2019, 60 (3), pp.636-647. ⟨10.1194/jlr.M091736⟩. ⟨hal-02140502⟩