Enriched PUFA environment of Leishmania infantum promastigotes promotes the accumulation of lipid mediators and favors parasite infectivity towards J774 murine macrophages
Résumé
Abstract Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We previously showed changes in the fatty acid composition (FA) of lipids in two strains of Leishmania donovani upon differentiation of promastigote to amastigote, including increased proportions of arachidonic acid (AA) and to a less extent of docosahexaenoic acid (DHA). Here, we carried out supplementation with AA or DHA on two Leishmania infantum strains, a visceral (MON‐1) and a cutaneous (MON‐24), to evaluate the role of these FA in parasite/macrophage interactions. The proportions of AA or DHA in total lipids were significantly increased in promastigotes cultured in AA‐ or DHA‐supplemented media compared to controls. The content of FA‐derived oxygenated metabolites was enhanced in supplemented strains, generating especially epoxyeicosatrienoic acids (11,12‐ and 14,15‐EET) and hydroxyeicosatetraenoic acids (5‐ and 8‐ HETE) from AA, and hydroxydocosahexaenoic acids (14‐ and 17‐HDoHE) from DHA. For both MON‐1 and MON‐24, AA‐supplemented promastigotes showed higher infectivity towards J774 macrophages as evidenced by higher intracellular amastigote numbers. Higher infectivity was observed after DHA supplementation for MON‐24 but not MON‐1 strain. ROS production by macrophages increased upon parasite infection, but only minor change was observed between control and supplemented parasites. We propose that under high AA or DHA environment that is associated with AA or DHA enrichment of promastigote lipids, FA derivatives can accumulate in the parasite, thereby modulating parasite infectivity towards host macrophages.
Mots clés
DHA
docosahexaenoic acid
FA
fatty acid
HDoHE
hydroxydocosahexaenoic acids
HETE
hydroxyeicosatetraenoic acids
LA
linoleic acid
MUFA
monounsaturated fatty acids
PG
prostaglandins
PUFA
polyunsaturated fatty acids
ROS
SFA
saturated fatty acids
VL
AA
arachidonic acid CL
Cutaneous leishmaniasis DHA
docosahexaenoic acid FA
fatty acid HDoHE
hydroxydocosahexaenoic acids HETE
hydroxyeicosatetraenoic acids LA
linoleic acid MUFA
monounsaturated fatty acids PG
prostaglandins PUFA
polyunsaturated fatty acids ROS
reactive oxygen species SFA
saturated fatty acids VL
visceral leishmaniasis lipid mediators
macrophages
reactive oxygen species
arachidonic acid
CL
Cutaneous leishmaniasis
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